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Health Technology Assessment 2010; Vol. 14: No. 37
Health Technology AssessmentNIHR HTA programmewww.hta.ac.uk
July 201010.3310/hta14370
A systematic review of photodynamic therapy in the treatment of pre-cancerous skin conditions, Barrett’s oesophagus and cancers of the biliary tract, brain, head and neck, lung, oesophagus and skin
D Fayter, M Corbett, M Heirs, D Fox and A Eastwood
Health Technology Assessment 2010; Vol. 14: No.371
Appendix 5 Pre-cancerous skin scoping
Appendix 6 Skin cancer scoping
Appendix 7 Barrett’s oesophagus scoping
Appendix 8 Oesophageal cancer scoping
Appendix 9 Lung cancer scoping
Appendix 10 Biliary tract cancer scoping
Appendix 11 Brain cancer scoping
Appendix 12 Head and neck cancer scoping
Appendix 13 Actinic keratosis data extraction
Appendix 14 Bowen’s disease data extraction
Appendix 15 Basal cell carcinoma data extraction
Appendix 16 Barrett’s oesophagus data extraction
Appendix 17 Oesophageal cancer data extraction
Appendix 18 Lung cancer data extraction
Appendix 19 Biliary tract cancer data extraction
Appendix 20 Brain cancer data extraction
Appendix 21 Head and neck cancer data extraction
Appendices Go to main text
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DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
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One hundred and thirty-three publications, with study designs that did not meet the inclusion
criteria for the review, reported on patients with pre-cancerous skin conditions being treated with PDT. The references are listed below, in alphabetical order; they have not been categorised and may still contain a number of duplicate publications.
References1. Alexiades-Armenakas MR, Bernstein LJ, Chen
J, Jacobson L, Geronemus R. Laser-assisted photodynamic therapy of actinic keratoses: long-term follow-up. Lasers Surg Med 2003;15(Suppl.):45.
2. Alexiades-Armenakas MR, Geronemus RG. Laser-mediated photodynamic therapy of actinic keratoses. Arch Dermatol 2003;139:1313–20.
3. Ammann R, Hunziker T. Photodynamic therapy for mycosis fungoides after topical photosensitization with 5-aminolevulinic acid. J Am Acad Dermatol 1995;33:541.
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7. Baptista J, Martinez C, Leite L, Cochito M. Our PDT experience in the treatment of non-melanoma skin cancer over the last 7 years. J Eur Acad Dermatol Venereol 2006;20:693–7.
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11. Berroeta L, Lewis-Jones MS, Evans AT, Ibbotson SH. Woringer-Kolopp (localized pagetoid reticulosis) treated with topical photodynamic therapy (PDT). Clin Exp Dermatol 2005;30:446–7.
12. Breuninger H, Bonnekoh B, Gollnick H. Photodynamic therapy with methylaminooxopentanoate (MetvixR) and a broad band light source (PhotoDyn 501): Experiences in complicated patients with actinic keratoses and basal cell carcinomas [Multiple letters]. JDDG (Journal of the German Society of Dermatology) 2005;3:397.
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Appendix 5 Pre-cancerous skin scoping
Appendix 5
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18. Calzavara-Pinton PG, Venturini M, Sala R, Capezzera R, Parrinello G, Specchia C, et al. Methylaminolaevulinate-based photodynamic therapy of Bowen’s disease and squamous cell carcinoma. Br J Dermatol 2008;159:137–44.
19. Calzavara-Pinton PG, Zane C, Facchetti F, Carlino A, Blanzuoli L, Marocolo D, et al. [Photodynamic therapy of non-melanoma skin tumours with topical delta-aminolevulinic acid.] G Ital Dermatol Venereol 1997;132:15–21.
20. Carruth JAS, Barrett JM, Barnes DWH, Buchanan RB, Sansom JM. A trial of photodynamic therapy for the treatment of tumors of the skin and head and neck, and the results of an experimental-study to determine the Interrelationships between the tissue effects of ionizing-radiation and photodynamic therapy. SPIE Proceedings Series 1993;1616:14–19.
21. Cavicchini S, Moretti D, Tanzi C, Tourlaki A. MAL-PDT in “difficult to treat’’ Bowen’s disease. J Invest Dermatol 2006;126:S36.
22. Ceylan C, Erboz S, Ozdemir F, Alper S. Topical photodynamic therapy for intraepidermal epithelioma. J Eur Acad Dermatol Venereol 2002;16:292–4.
23. Ceylan C, Erboz S, Ozdemir F, Kazandi A. [The effectiveness of topical photodynamic therapy in actinic.] Deri Hast Frengi Ars 2001;35:213–18.
24. Cochito M, Campos Lopes JM, Leite L. Topical photodynamic therapy in a case of Bowen’s disease of the face. Skin Cancer 1996;11:215–18.
25. Counters J, Zelickson B, Coles C, Selim M. A comparison of the V-beam and IPL in photodynamic therapy for reduction of actinic keratosis. Lasers Surg Med 2004;34:42.
26. de Haas ER, Sterenborg HJ, Neumann HA, Robinson DJ. The influence of light fractionation on the response of superficial skin cancer to aminolevulinic-acid photodynamic therapy. J Invest Dermatol 2006;126:S73.
27. de Haas ERM, de Vijlder HC, Sterenborg HJCM, Neumann HAM, Robinson DJ. Fractionated aminolevulinic acid-photodynamic therapy provides additional evidence for the use of PDT for non-melanoma skin cancer. J Eur Acad Dermatol Venereol 2008;22:426–30.
28. Dijkstra AT, Majoie IM, van Dongen JW, van Weelden H, van Vloten WA. Photodynamic therapy with violet light and topical 6-aminolaevulinic acid in the treatment of actinic keratosis, Bowen’s
disease and basal cell carcinoma. J Eur Acad Dermatol Venereol 2001;15:550–4.
29. Dragieva G, Hafner J, Dummer R, Schmid-Grendelmeier P, Roos M, Prinz BM, et al. Topical photodynamic therapy in the treatment of actinic keratoses and Bowen’s disease in transplant recipients. Transplantation 2004;77:115–21.
30. Erboz S, Ceylan C, Ozdemir F, Kazandi A, Ozol A. [Photodynamic treatment in solar keratosis.] Deri Hast Frengi Ars 1999;33:75–8.
31. Fernandez-Guarino M, Harto A, Perez-Garcia B, Martin-Gonzalez M, Urrutia S, Jaen P. Photodynamic therapy in disseminated superficial actinic porokeratosis. J Eur Acad Dermatol Venereol 2009;23:176–7.
32. Fijan S, Honigsmann H, Ortel B. Photodynamic therapy of epithelial skin tumours using delta-aminolaevulinic acid and desferrioxamine. Br J Dermatol 1995;133:282–8.
33. Fink-Puches R, Hofer A, Smolle J, Kerl H, Wolf P. Primary clinical response and long-term follow-up of solar keratoses treated with topically applied 5-aminolevulinic acid and irradiation by different wave bands of light. J Photochem Photobiol B 1997;41:145–51.
34. Fowler JF, Jr, Zax RH. Aminolevulinic acid hydrochloride with photodynamic therapy: efficacy outcomes and recurrence 4 years after treatment. Cutis 2002;69:2–7.
35. Fritsch C, Stege H, Saalmann G, Goerz G, Ruzicka T, Krutmann J. Green light is effective and less painful than red light in photodynamic therapy of facial solar keratoses. Photodermatol Photoimmunol Photomed 1997;13:181–5.
36. Gniazdowska B, Rueff F, Hillemanns P, Przybilla B. Allergic contact dermatitis from delta-aminolevulinic acid used for photodynamic therapy. Contact Dermatitis 1998;38:348–9.
37. Gold MH. Treatment of actinic cheilitis using photodynamic therapy with methylaminolevulinate: report of three cases [Commentary]. Dermatol Surg 2005;31:1348.
38. Goldman M, Atkin D. ALA/PDT in the treatment of actinic keratosis: spot versus confluent therapy. J Cosmetic Laser Ther 2003;5:107–10.
39. Gonzalez-Perez R, Garcia JG, Badiola IB, Calleja JMV, Sanchez SA, Diaz-Perez JL. [Topical photodynamic therapy with 5-amino levulinic acid: Experience at the Hospital of Cruces.] Actas Dermosifiliogr 1997;88:561–5.
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40. Guarneri C, Vaccaro M. Erosive pustular dermatosis of the scalp following topical methylaminolaevulinate photodynamic therapy. J Am Acad Dermatol 2009;60:521–2.
41. Gupta G, Morton CA, Whitehurst C, Moore JV, MacKie RM. Photodynamic therapy with meso-tetra(hydroxyphenyl) chlorin in the topical treatment of Bowen’s disease and basal cell carcinoma. Br J Dermatol 1999;141:385–6.
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43. Hauschild A, Lischner S, Lange-Asschenfeldt B, Egberts F. Treatment of actinic cheilitis using photodynamic therapy with methyl aminolevulinate: report of three cases. Dermatol Surg 2005;31:1344–7.
44. Hegyi J, Frey T, Arenberger P. The treatment of unilesional mycosis fungoides with methyl aminolevulinate-photodynamic therapy. J Eur Acad Dermatol Venereol 2008;22:1134–5.
45. Hyung SK, Jong YY, Kwang HC, Oh SK, Sang EM, Vinciullo C. Topical photodynamic therapy using intense pulsed light for treatment of actinic keratosis: clinical and histopathologic evaluation [Commentary]. Dermatol Surg 2005;31:33–7.
46. Itoh Y, Ninomiya Y, Henta T, Tajima S, Ishibashi A. Topical delta-aminolevulinic acid-based photodynamic therapy for Japanese actinic keratoses. J Dermatol 2000;27:513–18.
47. Jeffes EW, McCullough JL, Weinstein GD, Fergin PE, Nelson JS, Shull TF, et al. Photodynamic therapy of actinic keratosis with topical 5-aminolevulinic acid. A pilot dose-ranging study. Arch Dermatol 1997;133:727–32.
48. Jiraskova M, Jirasek L, Stork J, Vosmik F, Jirsa M. [Photodynamic diagnosis and therapy in dermatology. Experience with use of TPPS4 in skin diseases.] Cas Lek Cesk 2003;142:493–9.
49. Jiraskova M, Vosmik F, Krajsova I, Lapes M, Jirsa M. [Experience with photodynamic therapy in some skin affections.] Cesk Dermatol 1999;74:161–7.
50. Jiraskova M, Vosmik F, Lapes M, Jirsa M, Stadnik B. Experiences with local photodynamic therapy with TPPS4 and non-coherent light. Biomed Tech 1997;42(Suppl.):447–8.
51. Jones CM, Mang T, Cooper M, Wilson BD, Stoll HL, Jr. Photodynamic therapy in the treatment of Bowen’s disease. J Am Acad Dermatol 1992;27:979–82.
52. Jungersted JM, Dam TN, Bryld LE, Agner T. Allergic reactions to Metvix (ALA-ME). Contact Dermatitis 2008;58:184–6.
53. Kaae J, Philipsen PA, Haedersdal M, Wulf HC. Immediate whealing urticaria in red light exposed areas during photodynamic therapy. Acta Dermatol Venereol 2008;88:480–3.
54. Kacerovska D, Pizinger K, Majer F, Smid F. Photodynamic therapy of nonmelanoma skin cancer with topical hypericum perforatum extract: a pilot study. Photochem Photobiol 2008;84:779–85.
55. Kacerovska D, Pizinger K, Resl V, Cetkovska P, Jirsa M, Smid F. [Comparison of efficacy between the two photosensitizers in the photodynamic therapy of cutaneous tumours.] Cesko Dermatol 2006;81:148–52.
56. Karrer S, Baumler W, Abels C, Hohenleutner U, Landthaler M, Szeimies RM. Long-pulse dye laser for photodynamic therapy: investigations in vitro and in vivo. Lasers Surg Med 1999;25:51–9.
57. Karrer S, Szeimies RM, Landthaler M. Topical photodynamic therapy with 5-ala in the treatment of arsenic-induced skin tumors. SPIE Proceedings Series 1995;2371:222–5.
58. Karrer S, Szeimies RM, Sauerwald A, Landthaler M. Topical photodynamic therapy with 5-aminolevulinic acid in the treatment of actinic keratoses: a first clinical study. SPIE Proceedings Series 1996;2625:48–50.
59. Kasche A, Luderschmidt S, Ring J, Hein R. Photodynamic therapy induces less pain in patients treated with methyl aminolevulinate compared to aminolevulinic acid. J Drugs Dermatol 2006;5:353–6.
60. Kawczyk-Krupka A, Sieron A, Suwata-Jurczyk B, Adamek M. [Photodynamic therapy (PDT) using topically applied delta-aminolevulinic acid (ALA) for the treatment of malignant skin tumours.] Przegl Dermatol 2000;87:235–40.
61. Kerr AC, Ferguson J, Ibbotson SH. Acute phototoxicity with urticarial features during topical 5-aminolaevulinic acid photodynamic therapy. Clin Exp Dermatol 2007;32:201–2.
62. Kim EH, Kang HY, Lee E-S, Kim YC. Mycosis fungoides showing inCR to topical 5-aminolaevulinic acid phototherapy. Eur J Dermatol 2007;17:343–5.
63. Kim HS, Song KH, Kim KH. [Photodynamic therapy of actinic keratoses using 585nm dye laser and variable lights.] Korean J Dermatol 2005;43:53–9.
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65. Kodama M, Watanabe D, Akita Y, Tamada Y, Matsumoto Y. Photodynamic therapy for the treatment of actinic cheilitis. Photodermatol Photoimmunol Photomed 2007;23:209–10.
66. Kreutzer K, Bonnekoh B, Franke I, Gollnick H. [Photodynamic therapy with methylaminooxopentanoate (Metvix) and a broad band light source (PhotoDyn 501): practical experiences in problem-patients with actinic keratoses and basal cell carcinomas.] JDDG (Journal of the German Society of Dermatology) 2004;2:992–9.
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68. Lee JS, Kim YJ, Kang HY, Lee ES, Oh CH, Kim YC. [Topical photodynamic therapy for treatment of actinic keratosis using light-emitting diode (LED) device.] Korean J Dermatol 2005;43:469–74.
69. Loncaster JA, Moore JV, Allan D, Allan E. An ultrasound analysis of the response of Gorlin syndrome-related and sporadic basal cell carcinomas to aminolaevulinic acid photodynamic therapy. Photodiag Photodyn Ther 2005;2:149–55.
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75. Meijnders PJN, Star WM, De Bruijn RS, Treurniet-Donker AD, Van Mierlo MJM, Wijthoff SJM, et al. Clinical results of photodynamic therapy for superficial skin malignancies or actinic keratosis using topical 5-aminolaevulinic acid. Lasers Med Sci 1996;11:123–31.
76. Morton CA, Whitehurst C, McColl JH, Moore JV, MacKie RM. Photodynamic therapy for large or multiple patches of Bowen disease and basal cell carcinoma. Arch Dermatol 2001;137:319–24.
77. Morton CA, Whitehurst C, Moseley H, Moore JV, Mackie RM. Development of an alternative light source to lasers for photodynamic therapy: 3. Clinical evaluation in the treatment of pre-malignant non-melanoma skin cancer. Lasers Med Sci 1995;10:165–71.
78. Moseley H, Allen JW, Ibbotson S, Lesar A, McNeill A, Camacho-Lopez MA, et al. Ambulatory photodynamic therapy: a new concept in delivering photodynamic therapy. Br J Dermatol 2006;154:747–50.
79. Moseley H, Ibbotson S, Woods J, Brancaleon L, Lesar A, Goodman C, et al. Clinical and research applications of photodynamic therapy in dermatology: experience of the Scottish PDT Centre. Lasers Surg Med 2006;38:403–16.
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81. Nayeemuddin FA, Wong M, Yell J, Rhodes LE. Topical photodynamic therapy in disseminated superficial actinic porokeratosis. Clin Exp Dermatol 2002;27:703–6.
82. Paoli J, Halldin C, Ericson MB, Wennberg AM. Nerve blocks provide effective pain relief during topical photodynamic therapy for extensive facial actinic keratoses. Clin Exp Dermatol 2008;33:559–64.
83. Park SY, Kim KT, Yoon TJ. [A case of actinic keratosis treated by topical photodynamic therapy with low intensity dye laser.] Korean J Dermatol 2006;44:636–8.
84. Parlette EC. Red light laser photodynamic therapy of Bowen’s disease. J Drugs Dermatol 2004;3:S22–4.
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86. Perrett CM, McGregor J, Proby C, Harwood C. A comparative study of topical 5-fluorouracil and topical photodynamic therapy using methylaminolevulinate for actinic keratosis and Bowen’s disease in organ transplant recipients. J Am Acad Dermatol 2006;54:A7.
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93. Robinson PJ, Carruth JA, Fairris GM. Photodynamic therapy: a better treatment for widespread Bowen’s disease. Br J Dermatol 1988;119:59–61.
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95. Runfola MA, Weber TK, Rodriguez-Bigas MA, Dougherty TJ, Petrelli NJ. Photodynamic therapy for residual neoplasms of the perianal skin. Dis Colon Rectum 2000;43:499–502.
96. Sandberg C, Stenquist B, Rosdahl I, Ros A-M, Synnerstad I, Karlsson M, et al. Important factors for pain during photodynamic therapy for actinic keratosis. Acta Dermatol Venereol 2006;86:404–8.
97. Sega GM, Keohane SG. MAL-PDT in the treatment of ‘field changes’ in patients with
previous nonmelanoma skin cancer. Br J Dermatol 2005;153:96.
98. Shim SD, Kim YC, Chung PS, Rhee CK. [A case of actinic keratosis treated with topical photodynamic therapy with a 632 nm diode laser.] Korean J Dermatol 2004;42:1221–4.
99. Sieron A, Kawczyk-Krupka A, Wojciech Cebula MA, Szygula M, Zieleznik W, Gruk M, et al. Photodynamic therapy (PDT) using topically applied delta-aminolevulinic acid (ALA) for the treatment of malignant skin tumors. Photodiag Photodyn Ther 2004;1:311–17.
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101. Souza CS, Felicio LBA, Bentley MV, Tedesco AC, Ferreira J, Kurachi C, et al. Topical photodynamic therapy for Bowen’s disease of the digit in epidermolysis bullosa. Br J Dermatol 2005;153:672–4.
102. Stables GI, Stringer MR, Robinson DJ, Ash DV. Large patches of Bowen’s disease treated by topical aminolaevulinic acid photodynamic therapy. Br J Dermatol 1997;136:957–60.
103. Stables GI, Stringer MR, Robinson DJ, Ash DV. The treatment of Bowen’s disease by topical aminolaevulinic acid photodynamic therapy. Br J Dermatol 1998;139:74.
104. Stender IM, Wulf HC. Photodynamic therapy with 5-aminolevulinic acid in the treatment of actinic cheilitis. Br J Dermatol 1996;135:454–6.
105. Svanberg K, Andersson T, Killander D, Wang I, Stenram U, Andersson-Engels S, et al. Photodynamic therapy of non-melanoma malignant tumours of the skin using topical delta-amino levulinic acid sensitization and laser irradiation. Br J Dermatol 1994;130:743–51.
106. Szeimies RM, Karrer S, Sauerwald A, Landthaler M. Photodynamic therapy with topical application of 5-aminolevulinic acid in the treatment of actinic keratoses: an initial clinical study. Dermatology 1996;192:246–51.
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109. Tan B, Sinclair R, Foley P. Photodynamic therapy for subungual Bowen’s disease. Australas J Dermatol 2004;45:172–4.
110. Toll A, Parera Ma E, Velez M, Pujol RM. Photodynamic therapy with methyl aminolevulinate induces phototoxic reactions on areas of the nose adjacent to basal cell carcinomas and actinic keratoses. Dermatol Surg 2008;34:1145–7.
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113. Touma D, Yaar M, Whitehead S, Konnikov N, Gilchrest BA. A trial of short incubation, broad-area photodynamic therapy for facial actinic keratoses and diffuse photodamage. Arch Dermatol 2004;140:33–40.
114. Tschen E, Pariser D, Wong DS, Dunlap FE. Photodynamic therapy using aminolevulinic acid for patients with nonhyperkeratotic actinic keratoses of the face and scalp: long-term histopathologic results of a phase IV multicenter clinical trial. J Am Acad Dermatol 2005;52:P164.
115. Tschen EH, Wong DS, Pariser DM, Dunlap FE, Houlihan A, Ferdon MB, et al. Photodynamic therapy using aminolaevulinic acid for patients with nonhyperkeratotic actinic keratoses of the face and scalp: phase IV multicentre clinical trial with 12-month follow-up. Br J Dermatol 2006;155:1262–9.
116. Usmani N, Stables GI, Telfer NR, Stringer MR. Subungual Bowen’s disease treated by topical aminolevulinic acid-photodynamic therapy. J Am Acad Dermatol 2005;53:S273–6.
117. Usmani N, Telfer N, Stringer M, Stables G. Subungual Bowen’s disease treated by topical photodynamic therapy. J Am Acad Dermatol 2005;52:P164.
118. Vaicova M, Ettler K. [Our clinical experience with the use of photodynamic therapy in patients with the basal cell carcinoma and morbus Bowen (comparison of efficacy of two photosensitizers).] Cesk Dermatol 2004;79:200–4.
119. Varma S, Anstey A, Wilson H, Kurwa HA. Photodynamic therapy for the treatment of Bowen’s disease, solar keratoses, and superficial basal cell carcinomas: 12 months experience with a novel light source. Br J Dermatol 1998;139:19.
120. Varma S, Wilson H, Kurwa HA, Charman C. One year relapse rates for Bowen’s disease, basal cell carcinomas and solar keratoses treated by photodynamic therapy: analysis of 189 lesions. Br J Dermatol 1999;141:114–18.
121. Varma S, Wilson H, Kurwa HA, Gambles B, Charman C, Pearse AD, et al. Bowen’s disease, solar keratoses and superficial basal cell carcinomas treated by photodynamic therapy using a large-field incoherent light source. Br J Dermatol 2001;144:567–74.
122. Wang J, Gao M, Wen S, Wang M. Photodynamic therapy for 50 patients with skin cancers or precancerous lesions. Chin Med Sci J 1991;6:163–5.
123. Wang JB, Gao ML, Wen SJ, Wang MJ. Study of photodynamic therapy in skin cancers and precancerous lesions. SPIE Proceedings Series 1993;1616:139–42.
124. Wang XL, Wang HW, Guo MX, Xu SZ. Treatment of skin cancer and pre-cancer using topical ALA-PDT: a single hospital experience. Photodiag Photodyn Ther 2008;5:127–33.
125. Weisser H, Meyer-Rogge D, Meyer-Rogge E. [First experiences in medical practice with the new topical photosensitizer MAOP for actinic keratosis and basal cell carcinoma.] Aktuelle Dermatologie 2004;30:306–11.
126. Wennberg AM, Lindholm LE, Alpsten M, Larko O. Treatment of superficial basal cell carcinomas using topically applied delta-aminolaevulinic acid and a filtered xenon lamp. Arch Dermatol Res 1996;288:561–4.
127. Wolf P, Fink-Puches R, Cerroni L, Kerl H. Photodynamic therapy for mycosis fungoides after topical photosensitization with 5-aminolevulinic acid. J Am Acad Dermatol 1994;31:678–80.
128. Wolf P, Fink-Puches R, Reimann-Weber A, Kerl H. Development of malignant melanoma after repeated topical photodynamic therapy with 5-aminolevulinic acid at the exposed site. Dermatology 1997;194:53–4.
129. Wolf P, Rieger E, Kerl H. Topical photodynamic therapy with endogenous porphyrins after application of 5-aminolevulinic acid. An alternative treatment modality for solar keratoses,
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superficial squamous cell carcinomas, and basal cell carcinomas? [Erratum published in J Am Acad Dermatol 1993;29(1):41.] J Am Acad Dermatol 1993;28:17–21.
130. Wolfe CM, Hatfield K, Cognetta AB, Jr. Cellulitis as a postprocedural complication of topical 5-aminolevulinic acid photodynamic therapy in the treatment of actinic keratosis. J Drugs Dermatol 2007;6:544–8.
131. Wong TW, Sheu HM, Lee JY, Fletcher RJ. Photodynamic therapy for Bowen’s disease
(squamous cell carcinoma in situ) of the digit. Dermatol Surg 2001;27:452–6.
132. Xu S, Wang X, Xu W. [Evaluation of photodynamic therapy of skin cancers with delta-aminolevulinic acid.] Med J Wuhan Univ 2003;24:86–9.
133. Zelickson B, Coles C. Treatment of actinic keratosis with PDT and chemical light patch. Lasers Surg Med 2003;15(Suppl.):167.
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Two hundred and thirty-five publications, with study designs that did not meet the inclusion
criteria for the review, reported on patients with skin cancer being treated with PDT. The references are listed below in alphabetical order; they have not been categorised and may still contain a number of duplicate publications.
References1. Abels C, Karrer S, Baumler W, Goetz AE,
Landthaler M, Szeimies RM. Indocyanine green and laser light for the treatment of AIDS-associated cutaneous Kaposi’s sarcoma. Br J Cancer 1998;77:1021–4.
2. Alecu M, Ursaciuc C, Halalau F, Coman G, Merlevede W, Waelkens E, et al. Photodynamic treatment of basal cell carcinoma and squamous cell carcinoma with hypericin. Anticancer Res 1998;18:4651–4.
3. Allison RR, Mang TS, Wilson BD, Vongtama V. Tin ethyl etiopurpurin-induced photodynamic therapy for the treatment of human immunodeficiency virus-associated Kaposi’s sarcoma. Curr Ther Res Clin Exp 1998;59:23–7.
4. Alvanopoulos K, Antoniou C, Melpo P, Vareltzidis A, Katsambas A. Photodynamic therapy of superficial basal cell carcinomas using exogenous 5-aminolevulinic acid and 514-nm light. J Eur Acad Dermatol Venereol 1997;9:134–6.
5. Antoniou C, Katsambas A, Rigopoulos D, Palaskas E, Tsikrikas GN. Aminolevulinic acid: topical photodynamic therapy in skin cancers and solar keratoses. Skin Cancer 1996;11:81–4.
6. Attili S, Cochrane A, McNeill A, Camacho-Lopez M, Moseley H, Ibbotson S, et al. An open pilot study of ambulatory photodynamic therapy using a wearable, low-irradiance, organic LED light source in the treatment of nonmelanoma skin cancer. Br J Dermatol 2008;159:130–1.
7. Baas P, Saarnak AE, Oppelaar H, Neering H, Stewart FA. Photodynamic therapy with meta-tetrahydroxyphenylchlorin for basal cell carcinoma: a phase I/II study. Br J Dermatol 2001;145:75–8.
8. Bagnato VS, Kurachi C, Ferreira J, Marcassa LG, Sibata CH, Allison RR. PDT experience in
Brazil: a regional profile. Photodiag Photodyn Ther 2005;2:107–18.
9. Bakos RM, Bakos L, Ferlin E, Cestari T, Orlandini T, Rezende R, et al. [Photodynamic therapy with delta-aminolevulinic acid for superficial keratinocytic neoplasms.] An Bras Dermatol 2003;78:197–207.
10. Bandieramonte G, Marchesini R, Melloni E, Andreoli C, di Pietro S, Spinelli P, et al. Laser phototherapy following HpD administration in superficial neoplastic lesions. Tumori 1984;70:327–34.
11. Baptista J, Martinez C, Leite L, Cochito M. Our PDT experience in the treatment of non-melanoma skin cancer over the last 7 years. J Eur Acad Dermatol Venereol 2006;20:693–7.
12. Baron E, Domingo DS, Hsia A, Colussi V, Oleinick N, Foster T, et al. Silicon phthalocyanine photodynamic therapy for treatment of cutaneous neoplasms. J Invest Dermatol 2008;128:395.
13. Baron ED, Hanneman K, Scull HM, Hsia A, McCormick T, Oleinick NL, et al. Silicon phthalocyanine (Pc 4) photodynamic therapy for the treatment of pre-malignant and malignant skin conditions: an update. J Invest Dermatol 2005;125:942.
14. Bendsoe N, Persson L, Johansson A, Axelsson J, Svensson J, Grafe S, et al. Fluorescence monitoring of a topically applied liposomal Temoporfin formulation and photodynamic therapy of nonpigmented skin malignancies. J Environ Pathol Tox 2007;26:117–26.
15. Bendsoe N, Persson L, Johansson A, Axelsson J, Svensson J, Grafe S, et al. Fluorescence monitoring of a topically applied liposomal temoporfin formulation and photodynamic therapy of nonpigmented skin malignancies. J Environ Pathol Tox 2007;26:117–26.
16. Bernstein ZP, Wilson BD, Oseroff AR, Jones CM, Dozier SE, Brooks JS, et al. Photofrin photodynamic therapy for treatment of AIDS-related cutaneous Kaposi’s sarcoma. AIDS 1999;13:1697–704.
17. Betz CS, Rauschning W, Stranadko EP, Riabov MV, Albrecht V, Nifantiev NE, et al. Optimization of treatment parameters for Foscan-PDT of basal cell carcinomas. Lasers Surg Med 2008;40:300–11.
Appendix 6 Skin cancer scoping
Appendix 6
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18. Biel MA. Photodynamic therapy and the treatment of malignancies of the head and neck. SPIE Proceedings Series 1995;2392:55–62.
19. Bieniek A, Fraczek M, Cislo M, Maj J, Szybejko-Machaj G, Barancewicz-Losek M, et al. [Cancer of the skin of the nose. Epidemiology and treatment.] Dermatol Klin 2007;9:165–9.
20. Bloznelyte L, Cepulis V, Ponomarev I, Dougherty TJ. Intra-arterial PDT and ordinary PDT in head and neck cancer. SPIE Proceedings Series 1996;2675:76–9.
21. Bloznelyte L, Garlaite D, Felinskaite E. Differences of Photodamage in various malignant tissues which appear after application of Photodynamic therapy, using different laser systems. SPIE Proceedings Series 1995;2392:106–10.
22. Bogelund FS, Philipsen PA, Gniadecki R. Factors affecting the recurrence rate of basal cell carcinoma. Acta Dermatol Venereol 2007;87:330–4.
23. Breuninger H, Bonnekoh B, Gollnick H. [Photodynamic therapy with methylaminooxopentanoate (MetvixR) and a broad band light source (PhotoDyn 501): Experiences in complicated patients with actinic keratoses and basal cell carcinomas (multiple letters).] JDDG (Journal of the German Society of Dermatology) 2005;3:397.
24. Buchanan RB, Carruth JA, McKenzie AL, Williams SR. Photodynamic therapy in the treatment of malignant tumours of the skin and head and neck. Eur J Surg Oncol 1989;15:400–6.
25. Cairnduff F, Stringer MR, Hudson EJ, Ash DV, Brown SB. Superficial photodynamic therapy with topical 5-aminolaevulinic acid for superficial primary and secondary skin cancer. Br J Cancer 1994;69:605–8.
26. Calista D, Coccia L. Photodynamic therapy for the treatment of in situ squamous cell carcinoma of the left eyelid. Int J Dermatol 2008;47:1319–21.
27. Calzavara F, Tomio L. Photodynamic therapy: clinical experience at the Department of Radiotherapy at Padova General Hospital. J Photochem Photobiol B 1991;11:91–5.
28. Calzavara-Pinton PG. Repetitive photodynamic therapy with topical delta-aminolaevulinic acid as an appropriate approach to the routine treatment of superficial non-melanoma skin tumours. J Photochem Photobiol B 1995;29:53–7.
29. Calzavara-Pinton PG, Venturini M, Sala R, Capezzera R, Parrinello G, Specchia C, et al.
Methylaminolaevulinate-based photodynamic therapy of Bowen’s disease and squamous cell carcinoma. Br J Dermatol 2008;159:137–44.
30. Calzavara-Pinton PG, Zane C, Capezzera R, Venturini M, Sala R. MAL-PDT of in situ, microinvasive and invasive squamous cell carcinoma. J Invest Dermatol 2007;127:S44.
31. Calzavara-Pinton PG, Zane C, Facchetti F, Carlino A, Blanzuoli L, Marocolo D, et al. [Photodynamic therapy of non-melanoma skin tumours with topical delta-aminolevulinic acid.] G Ital Dermatol Venereol 1997;132:15–21.
32. Campbell SM, Morton CA, Alyahya R, Horton S, Pye A, Curnow A. Clinical investigation of the novel iron-chelating agent, CP94, to enhance topical photodynamic therapy of nodular basal cell carcinoma. Br J Dermatol 2008;159:387–93.
33. Cappugi P, Massi D, Salvini MD. Nodular basal cell carcinoma of the nose treated by photodynamic therapy (PDT). Photodynamic Therapy and Photodiagnosis in Clinical Practice, Brixen/Bressanone, 7–11 October, 2008. Poster session – CD12.
34. Cappugi P, Mavilia L, Campolmi P, Reali EF, Mori M, Rossi R. New proposal for the treatment of nodular basal cell carcinoma with intralesional 5-aminolevulinic acid. J Chemother 2004;16:491–3.
35. Carruth JAS, Barrett JM, Barnes DWH, Buchanan RB, Sansom JM. A trial of photodynamic therapy for the treatment of tumors of the skin and head and neck, and the results of an experimental-study to determine the interrelationships between the tissue effects of ionizing-radiation and photodynamic therapy. SPIE Proceedings Series 1993;1616:14–19.
36. Castro García J, Rincón Duran N, Gordon Parra M, Marcano Olaizola A, Aranguren L. Terapia fotodinámica: en cáncer de la piel. Rev Venez Oncol 2007;19:3–19.
37. Ceylan C, Ozdemir F, Erboz S, Kazandi A, Ozol A. [Topical photodynamic treatment in basal cell carcinoma.] Deri Hast Frengi Ars 1999;33:153–7.
38. Chapas A, Zeltser R, Geronemus R, Gilchrest B. Intralesional photodynamic therapy of nonmelanoma skin cancer. Lasers Surg Med 2006;38:27.
39. Chapas AM, Gilchrest BA. Broad area photodynamic therapy for treatment of multiple basal cell carcinomas in a patient with nevoid basal cell carcinoma syndrome. J Drugs Dermatol 2006;5:3–5.
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40. Christensen E, Skogvoll E, Viset T, Warloe T, Sundstrom S. Photodynamic therapy with 5-aminolaevulinic acid, dimethylsulfoxide and curettage in basal cell carcinoma: a 6-year clinical and histological follow-up. J Eur Acad Dermatol Venereol 2009;23:58–66.
41. Clark C, Bryden A, Dawe R, Moseley H, Ferguson J, Ibbotson SH. Topical 5-aminolaevulinic acid photodynamic therapy for cutaneous lesions: outcome and comparison of light sources. Photodermatol Photoimmunol Photomed 2003;19:134–41.
42. de Haas ERM, de Vijlder HC, Sterenborg HJCM, Neumann HAM, Robinson DJ. Fractionated aminolevulinic acid-photodynamic therapy provides additional evidence for the use of PDT for non-melanoma skin cancer. J Eur Acad Dermatol Venereol 2008;22:426–30.
43. Devirgiliis V, Panasiti V, Curzio M, Gobbi S, Rossi M, Roberti V, et al. Complete remission of nodular basal cell carcinoma after combined treatment with photodynamic therapy and imiquimod 5% cream. Dermatol Online J 2008;14.
44. Dijkstra AT, Majoie IM, van Dongen JW, van Weelden H, van Vloten WA. Photodynamic therapy with violet light and topical 6-aminolaevulinic acid in the treatment of actinic keratosis, Bowen’s disease and basal cell carcinoma. J Eur Acad Dermatol Venereol 2001;15:550–4.
45. Domaniecki J, Stanowski E, Graczyk A, Kalczak M, Struzyna J, Kwasny M, et al. Photodynamic method used for the treatment of malignant melanoma and Merkel cell carcinoma. SPIE Proceedings Series 1997;3188:122–7.
46. Dougherty TJ, Cooper MT, Mang TS. Cutaneous phototoxic occurrences in patients receiving Photofrin. Lasers Surg Med 1990;10:485–8.
47. Dougherty TJ, Kaufman JE, Goldfarb A, Weishaupt KR, Boyle D, Mittleman A. Photoradiation therapy for the treatment of malignant tumors. Cancer Res 1978;38:2628–35.
48. Edstrom DW, Hedblad MA. Long-term follow-up of photodynamic therapy for mycosis fungoides. Acta Dermatol Venereol 2008;88:288–90.
49. Edstrom DW, Porwit A, Ros AM. Photodynamic therapy with topical 5-aminolevulinic acid for mycosis fungoides: clinical and histological response. Acta Dermatol Venereol 2001;81:184–8.
50. Eibenschutz L, Marenda S, Mariani G, Ferrari A, Silipo V, Catricala C. MAL-PDT for the treatment of large basal cell carcinomas. J Invest Dermatol 2006;126:S16.
51. El-Far M, Setate A, El-Maddawy M. First initial clinical application of photodynamic therapy (PDT) in Egypt: two case reports. Laser Life Sci 1998;8:27–35.
52. Elliott S, Keller G, Razum N, Parks J, White R, Seiler A. Photodynamic therapy of nonmelanoma skin-cancer using a ktp-pumped dye-laser. SPIE Proceedings Series 1993;1881:2–9.
53. Elliott SL. The incidence and etiology of nonmelanoma skin cancer and selected management with photodynamic therapy. Laser Nursing 1992;6:83–91.
54. Evtushenko VA, Soldatov AN, Vusik MV, Reimer IV. Treatment of basal-cellular skin cancer and heavy concomitant diseases by a photodynamic therapeutic method with a dye laser LITT-PDT. SPIE Proceedings Series 2007;6938:32.
55. Fai D. MAL-PDT for the treatment of multiple basal cell carcinomas in a patient with Gorlin-Goltz syndrome. J Invest Dermatol 2006;126:S34-S.
56. Fijan S, Honigsmann H, Ortel B. Photodynamic therapy of epithelial skin tumours using delta-aminolaevulinic acid and desferrioxamine. Br J Dermatol 1995;133:282–8.
57. Filonenko E, Sokolov V, Sukhin D. Fluorescent diagnostics and photodynamic therapy of malignant cutaneous tumours. Photodynamic Therapy and Photodiagnosis in Clinical Practice, Brixen/Bressanone, 7–11 October, 2008. Poster session – SPO5.
58. Fink-Puches R, Soyer HP, Hofer A, Kerl H, Wolf P. Long-term follow-up and histological changes of superficial nonmelanoma skin cancers treated with topical delta-aminolevulinic acid photodynamic therapy. Arch Dermatol 1998;134:821–6.
59. Fink-Puches R, Wolf P, Kerl H. Photodynamic therapy of superficial basal cell carcinoma by instillation of aminolevulinic acid and irradiation with visible light. Arch Dermatol 1997;133:1494–5.
60. Gaal M, Gyulai R, Baltas E, Kui R, Olah J, Kemeny L. [Photodynamic therapy in dermatooncology.] Orv Hetil 2007;148:2227–33.
61. Gayl Schweitzer V. Photofrin-mediated photodynamic therapy for treatment of aggressive head and neck nonmelanomatous skin tumors in elderly patients. Laryngoscope 2001;111:1091–8.
62. Ghaffar SA, Clements SE, Lear JT. Epidermoid cysts mimicking recurrence of superficial basal cell carcinoma following photodynamic therapy. Clin Exp Dermatol 2007;32:223–4.
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63. Gonzalez-Perez R, Garcia JG, Badiola IB, Calleja JMV, Sanchez SA, Diaz-Perez JL. [Topical photodynamic therapy with 5-amino levulinic acid: Experience at the Hospital of Cruces.] Actas Dermosifiliogr 1997;88:561–5.
64. Gregory GF, Hopper C, Fan K, Grant WE, Bown SG, Speight PM. Photodynamic therapy and lip vermilion dysplasia: a pilot study. Eur J Cancer 1995;5:346–7.
65. Guillen C, Sanmartin O, Escudero A, Botella-Estrada R, Sevila A, Castejon P. Photodynamic therapy for in situ squamous cell carcinoma on chronic radiation dermatitis after photosensitization with 5-aminolaevulinic acid. J Eur Acad Dermatol Venereol 2000;14:298–300.
66. Gupta G, Morton CA, Whitehurst C, Moore JV, MacKie RM. Photodynamic therapy with meso-tetra(hydroxyphenyl) chlorin in the topical treatment of Bowen’s disease and basal cell carcinoma. Br J Dermatol 1999;141:385–6.
67. Ha XW, Sun XM, Xie JG, Fan XJ, Zhang YH, Mei QC, et al. Clinical use of hematoporphyrin derivative in malignant tumors. Chin Med J 1983;96:754–8.
68. Haller JC, Cairnduff F, Slack G, Schofield J, Whitehurst C, Tunstall R, et al. Routine double treatments of superficial basal cell carcinomas using aminolaevulinic acid-based photodynamic therapy. Br J Dermatol 2000;143:1270–5.
69. Hanneken S, Sterzinger AA, Schulte KW, Reifenberger J. [Photodynamic therapy for a nevoid basal cell carcinoma syndrome.] Hautarzt 2005;56:363–4.
70. Harth Y, Bergman R, Gotfried V, Kimel S, Friedman-Birnbaum R. A case of basal cell carcinoma treated with photodynamic therapy: changes in histological features and bcl-2 expression. J Eur Acad Dermatol Venereol 1996;7:163–6.
71. Harth Y, Hirshovitz B. [Topical photodynamic therapy in basal and squamous cell carcinoma and penile Bowen’s disease with 20% aminolevulinic acid, and exposure to red light and infrared light.] Harefuah 1998;134:602–5.
72. Harth Y, Hirshowitz B, Kaplan B. Modified topical photodynamic therapy of superficial skin tumors, utilizing aminolevulinic acid, penetration enhancers, red light, and hyperthermia. Dermatol Surg 1998;24:723–6.
73. Hebeda KM, Huizing MT, Brouwer PA, van der Meulen FW, Hulsebosch HJ, Reiss P, et al.
Photodynamic therapy in AIDS-related cutaneous Kaposi’s sarcoma. J Acquir Immune Defic Syndr Hum Retrovirol 1995;10:61–70.
74. Heinritz H, Benzel W, Sroka R, Iro H. Photodynamic therapy of superficial skin tumors following local application of delta-aminolaevulinic acid. Adv Otorhinolaryngol 1995;49:48–52.
75. Hintschich C, Feyh J, Beyer-Machule C, Riedel K, Ludwig K. Photodynamic laser therapy of basal-cell carcinoma of the lid. Ger J Ophthalmol 1993;2:212–17.
76. Hoerauf H, Huttmann G, Diddens H, Thiele B, Laqua H. [Photodynamic therapy of eyelid basalioma after topical administration of delta-aminolevulinic acid.] Ophthalmologe 1994;91:824–9.
77. Horn M, Wolf P, Wulf HC, Warloe T, Fritsch C, Rhodes LE, et al. Topical methyl aminolaevulinate photodynamic therapy in patients with basal cell carcinoma prone to complications and poor cosmetic outcome with conventional treatment. Br J Dermatol 2003;149:1242–9.
78. Hunzelmann VVN, Kubler AC. [Systemical photodynamic therapy for the treatment of nodular basalioma (case-report).] Z Hautkrankheiten 2000;75:712–14.
79. Hurlimann AF, Hanggi G, Panizzon RG. Photodynamic therapy of superficial basal cell carcinomas using topical 5-aminolevulinic acid in a nanocolloid lotion. Dermatology 1998;197:248–54.
80. Isanov T, Graschew G, Shopova M, Mitrov G, Mitev U, Jori G. Photodynamic therapy for the treatment of skin cancer. A case report. Radiobiol Radiother 1987;28:5–7.
81. Itkin A, Gilchrest BA. Delta-aminolevulinic acid and blue light photodynamic therapy for treatment of multiple basal cell carcinomas in two patients with nevoid basal cell carcinoma syndrome. Dermatol Surg 2004;30:1054–61.
82. Itoh Y, Henta T, Ninomiya Y, Tajima S, Ishibashi A. Repeated 5-aminolevulinic acid-based photodynamic therapy following electro-curettage for pigmented basal cell carcinoma. J Dermatol 2000;27:10–15.
83. Jiraskova M, Jirasek L, Stork J, Vosmik F, Jirsa M. [Photodynamic diagnosis and therapy in dermatology. Experience with use of TPPS4 in skin diseases.] Cas Lek Cesk 2003;142:493–9.
84. Jiraskova M, Vosmik F, Krajsova I, Lapes M, Jirsa M. [Experience with photodynamic therapy in some skin affections.] Cesk Dermatol 1999;74:161–7.
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85. Jiraskova M, Vosmik F, Lapes M, Jirsa M, Stadnik B. Experiences with local photodynamic therapy with TPPS4 and non-coherent light. Biomed Tech 1997;42(Suppl.):447–8.
86. Jungersted JM, Dam TN, Bryld LE, Agner T. Allergic reactions to Metvix (ALA-ME). Contact Dermatitis 2008;58:184–6.
87. Kaae J, Philipsen PA, Haedersdal M, Wulf HC. Immediate whealing urticaria in red light exposed areas during photodynamic therapy. Acta Dermatol Venereol 2008;88:480–3.
88. Kacerovska D, Pizinger K, Majer F, Smid F. Photodynamic therapy of nonmelanoma skin cancer with topical hypericum perforatum extract: a pilot study. Photochem Photobiol 2008;84:779–85.
89. Kacerovska D, Pizinger K, Resl V, Cetkovska P, Jirsa M, Smid F. [Comparison of efficacy between the two photosensitizers in the photodynamic therapy of cutaneous tumours.] Cesk Dermatol 2006;81:148–52.
90. Kapinus VN, Kaplan MA. Photodynamic therapy of locally invasive cutaneous carcinoma. In: Laser Helsinki 2008, 13th International Congress of EMLA (European Medical Laser Association) in conjunction with EMLA Finland and MAL (Medical Acupuncture and Laser) in cooperation with ASLMS (American Society for Laser Medicine and Surgery); 2008; Helsinki. 2008.
91. Karagas MR, Stukel TA, Umland V, Tsoukas MM, Mott LA, Sorensen HT, et al. Reported use of photosensitizing medications and basal cell and squamous cell carcinoma of the skin: results of a population-based case-control study. J Invest Dermatol 2007;127:2901–3.
92. Karrer S, Szeimies RM, Hohenleutner U, Heine A, Landthaler M. Unilateral localized basaliomatosis: treatment with topical photodynamic therapy after application of 5-aminolevulinic acid. Dermatology 1995;190:218–22.
93. Karrer S, Szeimies RM, Landthaler M. Topical photodynamic therapy with 5-ala in the treatment of arsenic-induced skin tumors. SPIE Proceedings Series 1995;2371:222–5.
94. Kaviani A, Ataie-Fashtami L, Fateh M, Sheikhbahaee N, Ghodsi M, Zand N, et al. Photodynamic therapy of head and neck basal cell carcinoma according to different clinicopathologic features. Lasers Surg Med 2005;36:377–82.
95. Kawczyk-Krupka A, Sieron A, Suwata-Jurczyk B, Adamek M. [Photodynamic therapy (PDT) using topically applied delta-aminolevulinic acid (ALA) for the treatment of malignant skin tumours.] Przegl Dermatol 2000;87:235–40.
96. Keller GS, Razum NJ, Doiron DR. Photodynamic therapy for nonmelanoma skin cancer. Facial Plast Surg 1989;6:180–4.
97. Kennedy J. HPD photoradiation therapy for cancer at Kingston and Hamilton. Adv Exp Med Biol 1983;160:53–62.
98. Kennedy JC, Pottier RH, Pross DC. Photodynamic therapy with endogenous protoporphyrin IX: basic principles and present clinical experience. J Photochem Photobiol B 1990;6:143–8.
99. Keohane S. Successful clearance of residual superficial basal cell carcinoma with MAL-PDT following Mohs surgery. J Am Acad Dermatol 2005;52:P164-P.
100. Kerr AC, Ferguson J, Ibbotson SH. Acute phototoxicity with urticarial features during topical 5-aminolaevulinic acid photodynamic therapy. Clin Exp Dermatol 2007;32:201–2.
101. Konig K, Boehncke WH, Ruck A, Kaufmann R, Steiner R, Sterry W. Photodynamic effects on T-Cells and skin-lesions of a patient with mycosis fungoides using porphyrin photosensitizers. SPIE Proceedings Series 1994;2086:268–76.
102. Kopera D, Cerroni L, Fink-Puches R, Kerl H. Different treatment modalities for the management of a patient with the nevoid basal cell carcinoma syndrome. J Am Acad Dermatol 1996;34:937–9.
103. Kreutzer K, Bonnekoh B, Franke I, Gollnick H. [Photodynamic therapy with methylaminooxopentanoate (Metvix) and a broad band light source (PhotoDyn 501): practical experiences in problem-patients with actinic keratoses and basal cell carcinomas.] JDDG (Journal of the German Society of Dermatology) 2004;2:992–9.
104. Kubler AC, de Carpentier J, Hopper C, Leonard AG, Putnam G. Treatment of squamous cell carcinoma of the lip using Foscan-mediated photodynamic therapy. Int J Oral Maxillofac Surg 2001;30:504–9.
105. Kubler AC, Haase T, Staff C, Kahle B, Rheinwald M, Muhling J. Photodynamic therapy of primary nonmelanomatous skin tumours of the head and neck. Lasers Surg Med 1999;25:60–8.
106. Kuijpers DIM, Smeets NWJ, Krekels GAM, Thissen MRTM. Photodynamic therapy as adjuvant treatment of extensive basal cell carcinoma treated with Mohs micrographic surgery. Dermatol Surg 2004;30:794–8.
107. Lane JE, Allen JH, Lane TN, Lesher JL, Jr. Unilateral Basal cell carcinomas: an unusual entity
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Seven non-RCTs reported in 11 publications were identified, which reported on patients with
Barrett’s oesophagus being treated with PDT.1–11 These were originally to be included in the main systematic review; however, as 24 publications reporting 11 RCTs were identified, these less robust non-randomised designs were subsequently excluded from the review.
A further 96 publications with study designs that did not meet the inclusion criteria for the review were identified.12–107 The references are listed below in alphabetical order, they have not been categorised and may still contain a number of duplicate publications.
ReferencesNon-randomised controlled trials1. Gross SA, Gill KR, Wolfsen HC. Comparative
outcomes of photodynamic therapy and radiofrequency ablation for the treatment of Barrett’s esophagus with high grade dysplasia. Gastrointest Endosc 2008;67:A179.
2. Jamieson N, Mosse A, Thorpe S, Novelli M, Bown S, Lovat L. High-grade dysplasia in Barrett’s esophagus: successful ablation by photodynamic therapy with ALA requires intensive therapy. Gastroenterology 2003;124:A298.
3. Jamieson NF, Thorpe S, Mosse A, Bown SG, Lovat LB. High grade dysplasia in Barrett’s oesophagus: successful ablation by photodynamic therapy with ALA requires intensive therapy. Gut 2003;52:73.
4. Mackenzie G, Clark BR, Selvasekar C, Jamieson N, Novelli M, Thorpe S, et al. Photodynamic therapy with 5 aminolevulinic acid for high grade dysplasia in Barrett’s esophagus: longterm follow-up of 51 patients. Gastroenterology 2005;128:A238.
5. Mackenzie GD, Clark B, Selvasekar CR, Jamieson NF, Novelli MR, Thorpe SM, et al. Photodynamic therapy with 5 aminolevulinic acid for high grade dysplasia in Barrett’s oesophagus: long term follow-up of 51 patients. Gut 2005;54:53.
6. Mackenzie GD, Jamieson NF, Novelli MR, Mosse CA, Clark BR, Thorpe SM, et al. How light dosimetry influences the efficacy of photodynamic therapy with 5-aminolaevulinic acid for ablation of
high-grade dysplasia in Barrett’s esophagus. Lasers Med Sci 2008;23:203–10.
7. May A, Gossner L, Pech O, Fritz A, Gunter E, Mayer G, et al. Local endoscopic therapy for intraepithelial high-grade neoplasia and early adenocarcinoma in Barrett’s oesophagus: acute-phase and intermediate results of a new treatment approach. Eur J Gastroenterol Hepatol 2002;14:1085–91.
8. Mellidez JC, Mackenzie G, Selvasekar C, Novelli M, Thorpe S, Mosse C, et al. Reversal of Barrett’s esophagus following photodynamic therapy using high dose 5 aminolevulinic acid activated by red or green laser light. Gastroenterology 2005;128:A239.
9. Panjehpour M, Overholt BF, Phan MN, Haydek JM. Optimization of light dosimetry for photodynamic therapy of Barrett’s esophagus: efficacy vs. incidence of stricture after treatment. Gastrointest Endosc 2005;61:13–18.
10. Panjehpour M, Phan MN, Overholt BF, Haydek JM. Optimization of light dosimetry for photodynamic therapy of Barrett’s esophagus. SPIE Proceedings Series 2004;5315:100–6.
11. Phan MN, Panjehpour M, Overholt BF. Optimization of photodynamic therapy for Barrett’s esophagus: treatment efficacy and stricture incidence as a function of light dose. Gastroenterology 2004;126:A178.
Other scoping publications12. Photodynamic therapy with porfimer sodium
for ablation of high-grade dysplasia in Barrett’s esophagus: international, partially blinded, randomized phase III trial. [Erratum published in Gastrointest Endosc 2005;62:488–498.] Gastrointest Endosc 2006;63:359.
13. Ackroyd R, Brown NJ, Davis MF, Stephenson TJ, Stoddard CJ, Reed MW. Aminolevulinic acid-induced photodynamic therapy: safe and effective ablation of dysplasia in Barrett’s esophagus. Dis Esophagus 2000;13:18–22.
14. Ackroyd R, Brown NJ, Davis MF, Stephenson TJ, Stoddard CJ, Reed MWR. Aminolaevulinic acid-induced photodynamic therapy in the treatment of dysplastic Barrett’s oesophagus and adenocarcinoma. Lasers Med Sci 1999;14:278–85.
Appendix 7 Barrett’s oesophagus scoping
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15. Ackroyd R, Kelty CJ, Brown NJ, Stephenson TJ, Stoddard CJ, Reed MWR. Eradication of dysplastic Barrett’s oesophagus using photodynamic therapy: long-term follow-up. Endoscopy 2003;35:496–501.
16. Attila T, Kortan P, Kandel GT, Marcon N. Photodynamic therapy (PDT) for Barrett’s esophagus with high grade dysplasia (BE-HGD). Gastrointest Endosc 2005;61:A127.
17. Ban S, Mino M, Nishioka NS, Puricelli W, Zukerberg LR, Shimizu M, et al. Histopathologic aspects of photodynamic therapy for dysplasia and early adenocarcinoma arising in Barrett’s esophagus. Am J Surg Pathol 2004;28:1466–73.
18. Barr H, Shepherd NA, Dix A, Roberts DJ, Tan WC, Krasner N. Eradication of high-grade dysplasia in columnar-lined (Barrett’s) oesophagus by photodynamic therapy with endogenously generated protoporphyrin IX. Lancet 1996;348:584–5.
19. Barr H, Tan WC, Shepherd NA, Krasner N. Photodynamic therapy (PDT) using 5-aminolaevulinic acid (5ALA) for oesophageal adenocarcinoma associated with Barrett’s metaplasia. Lasers Med Sci 1997;12:291–2.
20. Behrens A, May A, Gossner L, Gunter E, Pech O, Vieth M, et al. Curative treatment for high-grade intraepithelial neoplasia in Barrett’s esophagus. Endoscopy 2005;37:999–1005.
21. Buttar NS, Wang KK, Lutzke LS, Krishnadath KK, Anderson MA. Combined endoscopic mucosal resection and photodynamic therapy for esophageal neoplasia within Barrett’s esophagus. Gastrointest Endosc 2001;54:682–8.
22. Chen WR, Huang Z, Korbelik M, Nordquist RE, Liu H. Photoimmunotherapy for cancer treatment. J Environ Pathol Tox 2006;25:281–91.
23. Etienne J, Canard JM. [Photodynamic therapy in liberal practice.] Acta Endoscopica 2007;37:397–8.
24. Etienne J, Dorme N, Bourg-Heckly G, Raimbert P, Fekete F. [Local curative treatment of superficial adenocarcinoma in Barrett’s esophagus. First results of photodynamic therapy with a new photosensitizer.] Bull Acad Natl Med 2000;184:1731–44; discussion 44–47.
25. Etienne J, Dorme N, Bourg-Heckly G, Raimbert P, Fekete F, Mercadier Mc, et al. Local curative treatment of superficial adenocarcinoma in Barrett’s esophagus. First results of photodynamic therapy with a new photosensitizer. Bull Acad Natl Med 2000;184:1731–47.
26. Etienne J, Dorme N, Bourg-Heckly G, Raimbert P, Flejou JF. Photodynamic therapy with green light and m-tetrahydroxyphenyl chlorin for intramucosal adenocarcinoma and high-grade dysplasia in Barrett’s esophagus. Gastrointest Endosc 2004;59:880–9.
27. Foroulis CN, Thorpe JAC. Photodynamic therapy (PDT) in Barrett’s esophagus with dysplasia or early cancer. Eur J Cardiothorac Surg 2006;29:30–4.
28. Globe J, Kelty CJ, Smythe A, Ackroyd R. The effect of photodynamic therapy (PDT) on oesophageal motility in Barrett’s oesophagus. Gut 2004;53:118.
29. Globe J, Smythe A, Kelty CJ, Reed MWR, Brown NJ, Ackroyd R. The effect of photodynamic therapy (PDT) on oesophageal motility and acid clearance in patients with Barrett’s oesophagus. J Photochem Photobiol B Biol 2006;85:17–22.
30. Go JT, Dumot JA, Lopez R, Vargo J, Zuccaro G, Falk G, et al. Photodynamic therapy in Barrett’s esophagus with high grade dysplasia and intra-mucosal carcinoma. Am J Gastroenterol 2006;101:66.
31. Gossner L, Stolte M, Sroka R, Rick K, May A, Hahn EG, et al. Photodynamic ablation of high-grade dysplasia and early cancer in Barrett’s esophagus by means of 5-aminolevulinic acid. Gastroenterology 1998;114:448–55.
32. Heller SJ, Van Dam J, Barr H. Eradication of high-grade dysplasia using 5-ALA and acid suppression: a (photo)dynamic duo. Gastroenterology 1997;112:2156–8.
33. Hemminger LL, Wolfsen HC. Photodynamic therapy for Barrett’s esophagus and high grade dysplasia: results of a patient satisfaction survey. Gastroenterol Nurs 2002;25:139–41.
34. Hinnen P, de Rooij FWM, Hop WCJ, Edixhoven A, van Dekken H, Wilson JHP, et al. Timing of 5-aminolaevulinic acid-induced photodynamic therapy for the treatment of patients with Barrett’s oesophagus. J Photochem Photobiol B Biol 2002;68:8–14.
35. Hur C, Wittenberg E, Nishioka NS, Gazelle GS. Quality of life in patients with various Barrett’s esophagus associated health states. Health Qual Life Outcomes 2006;4:45.
36. Ikeguchi M, Lightdale CJ, Choi YA, Bukowski K. A new light delivery system for photodynamic therapy with aminolevulinic acid (ALA) for treatment of high-grade dysplasia in Barrett’s esophagus. Gastrointest Endosc 2005;61:A233.
37. Jamieson N, Thorpe S, Mosse A, Novelli M, Lovat L, Bown S. Photodynamic therapy using mTHPC
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for early Barrett’s-associated esophageal cancer. Gastroenterology 2003;124:A298.
38. Jamieson NF, Thorpe S, Masse A, Bown SG, Lovat LB. Photodynamic therapy using mTHPC for early Barrett’s-associated oesophageal cancers. Gut 2003;52:170.
39. Javaid B, Watt P, Krasner N. Photodynamic therapy (PDT) for oesophageal dysplasia and early carcinoma with mTHPC (m-tetrahydroxyphenyl chlorin): a preliminary study. Lasers Med Sci 2002;17:51–6.
40. Javaid B, Watt P, Krasner N, Brouwer PA. Oesophageal photodynamic therapy with mTHPC (m-tetra hydroxyphenyl chlorin) using a laser and a non-laser light source: a pilot study. SPIE Proceedings Series 2001;4156:262–5.
41. Jenkins JT, Charles A, Mitchell KG, Fullarton GM. Photodynamic therapy for Barretts’ adenocarcinoma associated with an Angelchik device. Photodiag Photodyn Ther 2005;2:197–200.
42. Kashtan H, Umansky M, Birkenfeld S, Scherubl H, Haddad R, Greenberg R, et al. Photodynamic therapy of Barrett’s esophagus with dysplasia using systemic aminolevulinic acid and a non-laser light source. A phase I/II study. Gastrointest Oncol 2002;4:153–7.
43. Kashtan H, Umansky M, Birkenfeld S, Scherubl H, Haddad R, Greenberg R, et al. Photodynamic therapy of Barrett’s esophagus with dysplasia using systemic aminolevulinic acid and a non-laser light source. A phase I/II study. Gastrointest Oncol 2002;4:153–8.
44. Keeley SB, Luketich JD, Landreneau RJ, Christie NA, Rivera MA, McGrath K. Using photodynamic therapy to cure esophageal cancer and Barrett’s high-grade dysplasia. Ann Surg Oncol 2006;13:85.
45. Keeley SB, Pennathur A, Gooding W, Landreneau RJ, Christie NA, Luketich J. Photodynamic therapy with curative intent for Barrett’s esophagus with high grade dysplasia and superficial esophageal cancer. Ann Surg Oncol 2007;14:2406–10.
46. Krishna M, Nakhleh RE, Hemminger LL, Wolfsen HC. Histologic characteristics and follow-up of 37 cases of Barrett’s esophagus with high grade dysplasia and intramucosal adenocarcinoma treated with photodynamic therapy. Lab Invest 2006;86:504.
47. Krishna M, Nakhleh RE, Hemminger LL, Wolfsen HC. Histologic characteristics and follow-up of 37 cases of Barrett’s esophagus with high grade dysplasia and intramucosal adenocarcinoma treated with photodynamic therapy. Mod Pathol 2006;19:504.
48. Krishnadath KK, Wang KK, Taniguchi K, Sebo TJ, Buttar NS, Anderson MA, et al. Persistent genetic abnormalities in Barrett’s esophagus after photodynamic therapy. Gastroenterology 2000;119:624–30.
49. Laukka MA, Wang KK. Initial results using low-dose photodynamic therapy in the treatment of Barrett’s esophagus. Gastrointest Endosc 1995;42:59–63.
50. Lovat LB, Jamieson NF, Novelli MR, Mosse CA, Selvasekar C, Mackenzie GD, et al. Photodynamic therapy with m-tetrahydroxyphenyl chlorin for high-grade dysplasia and early cancer in Barrett’s columnar lined esophagus. Gastrointest Endosc 2005;62:617–23.
51. Luketich JD, Fernando HC, Christie NA, Litle VR, Ferson PF, Buenaventura PO, et al. Photodynamic therapy in thoracic oncology: a single institution experience. SPIE Proceedings Series 2001;4248:28–33.
52. Macrae FA, Rajesekaram R, Thomas R, Bhathal PS. Photodynamic therapy in high grade dysplasia in Barrett’s oesophagus using 5 amino-laevulinic acid sensitization. Gastrointest Endosc 2004;59:A252.
53. Mino-Kenudosn M, Ban S, Deshpande V, Shimizu M, Lauwers GY. Buried dysplasia and early adenocarcinoma arising in Barrett esophagus (BE) after photodynamic therapy (PDT): not uncommon findings. Mod Pathol 2006;19:516.
54. Mino-Kenudson M, Ban S, Deshpande V, Shimizu M, Lauwers GY. Buried dysplasia and early adenocarcinoma arising in Barrett Esophagus (BE) after photodynamic therapy (PDT): not uncommon findings. Lab Invest 2006;86:114A.
55. Mino-Kenudson M, Ban S, Ohana M, Puricelli W, Deshpande V, Shimizu M, et al. Buried dysplasia and early adenocarcinoma arising in Barrett esophagus after porfimer-photodynamic therapy. Am J Surg Pathol 2007;31:403–9.
56. Mino-Kenudson M, Lauwers GY. Pathology of Barrett esophagus after photodynamic therapy. Mod Pathol 2007;20:550.
57. Moghissi K, Dixon K. The role of photodynamic therapy (PDT) in pre-malignant and malignant oesophageal lesions: can PDT compete with surgery? Laser Helsinki 2008, 13th International Congress of EMLA (European Medical Laser Association) in conjunction with EMLA Finland and MAL (Medical Acupuncture and Laser) in cooperation with ASLMS (American Society for Laser Medicine and Surgery), Helsinki, 2008.
58. Moghissi K, Dixon K, Thorpe JAC, Stringer MR. The role of photodynamic therapy (PDT)
Appendix 7
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in oesophageal pre-neoplastic and malignant neoplastic lesions of the oesophagus: a review study. Photodynamic Therapy and Photodiagnosis in Clinical Practice, Brixen/Bressanone. 7–11 October 2008. Session 6 – invited lecture.
59. Ohana M, Mino-Kenudson M, Ban S, Puricelli W, Nishioka N. Frequent persistence of dysplasia by systematic pathological evaluation after photodynamic therapy for Barrett’s esophagus with high-grade dysplasia or early adenocarcinoma. Gastroenterology 2005;129:1109.
60. Ohana M, Mino-Kenudson M, Ban S, Puricelli W, Nishoka N. Frequent persistence of dysplasia by systematic pathological evaluation after photodynamic therapy for Barrett’s Esophagus with high-grade dysplasia or early adenocarcinoma. Gastrointest Endosc 2005;61:A94.
61. Ohana M, Mino-Kenudson M, Ban SC, Puricelli W, Nishioka N, Lauwers G. Frequent persistence of dysplasia by systematic pathological evaluation after photodynamic therapy for Barrett’s Esophagus with high-grade dysplasia or early adenocarcinoma. Gastroenterology 2005;128:A72.
62. Ortner MA, Zumbusch K, Liebetruth J, Ebert B, Fleige B, Dietel M, et al. Is topical delta-aminolevulinic acid adequate for photodynamic therapy in Barrett’s esophagus? A pilot study. Endoscopy 2002;34:611–16.
63. Overholt B, Panjehpour M, Tefftellar E, Rose M. Photodynamic therapy for treatment of early adenocarcinoma in Barrett’s esophagus. Gastrointest Endosc 1993;39:73–6.
64. Overholt BF, Panjehpour M. Photodynamic therapy in Barrett’s esophagus: reduction of specialized mucosa, ablation of dysplasia, and treatment of superficial esophageal cancer. Semin Surg Oncol 1995;11:372–6.
65. Overholt BF, Panjehpour M. Barrett’s esophagus: photodynamic therapy for ablation of dysplasia, reduction of specialized mucosa, and treatment of superficial esophageal cancer. Gastrointest Endosc 1995;42:64–70.
66. Overholt BF, Panjehpour M. Barretts esophagus – photodynamic therapy for ablation of dysplasia, reduction of specialized mucosa and treatment of superficial esophageal cancer. SPIE Proceedings Series 1995;2371:375–84.
67. Overholt BF, Panjehpour M. Photodynamic therapy in Barrett’s esophagus. J Clin Laser Med Surg 1996;14:245–9.
68. Overholt BF, Panjehpour M. Photodynamic therapy for Barrett’s esophagus: clinical update. Am J Gastroenterol 1996;91:1719–23.
69. Overholt BF, Panjehpour M. Photodynamic therapy for Barrett’s esophagus. Gastrointest Endosc Clin N Am 1997;7:207–20.
70. Overholt BF, Panjehpour M, Ayres M. Photodynamic therapy for Barrett’s esophagus: cardiac effects. Lasers Surg Med 1997;21:317–20.
71. Overholt BF, Panjehpour M, Halberg DL. Photodynamic therapy for Barrett’s esophagus with dysplasia and/or early stage carcinoma: long-term results. Gastrointest Endosc 2003;58:183–8.
72. Overholt BF, Panjehpour M, Halberg DL. Photodynamic therapy for Barrett’s esophagus with dysplasia and/or early stage carcinoma: long-term results. Gastrointest Endosc 2003;58:183–8.
73. Overholt BF, Panjehpour M, Haydek JM. Photodynamic therapy for Barrett’s esophagus: follow-up in 100 patients. Gastrointest Endosc 1999;49:1–7.
74. Pacifico RJ, Wang KK, Wongkeesong L-M, Buttar NS, Lutzke LS. Combined endoscopic mucosal resection and photodynamic therapy versus esophagectomy for management of early adenocarcinoma in Barrett’s esophagus. Clin Gastroenterol Hepatol 2003;1:252–7.
75. Panjehpour M, Overholt BF, Dougherty TJ. Photodynamic therapy in Barrett’s esophagus: review of current results. SPIE Proceedings Series 1996;2675:20–8.
76. Panjehpour M, Overholt BF, Dougherty TJ. Photodynamic therapy of dysplasia in Barrett’s esophagus: an update. SPIE Proceedings Series 1997;2972:27–36.
77. Panjehpour M, Overholt BF, Haydek JM, Dougherty TJ. Photodynamic therapy with photofrin followed by thermal ablation for elimination of dysplasia and early cancer in Barrett’s esophagus: follow-up in 100 patients. SPIE Proceedings Series 1998;3247:14–24.
78. Panjehpour M, Overholt BF, Phan MN, Haydek JM, Robinson AF. Photodynamic therapy for Barrett’s esophagus using a 20-mm diameter light-delivery balloon (invited paper). SPIE Proceedings Series 2002;4612:13–20.
79. Panjehpour M, Phan MN, Overholt BF. Relationship between acute mucosal injury, treatment efficacy and esophageal stricture following photodynamic therapy of Barrett’s esophagus. Gastrointest Endosc 2004;59:A251.
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80. Pech O, Gossner L, May A, Rabenstein T, Vieth M, Stolte M, et al. Long-term results of photodynamic therapy with 5-aminolevulinic acid for superficial Barrett’s cancer and high-grade intraepithelial neoplasia. Gastrointest Endosc 2005;62:24–30.
81. Pech O, Gossner L, May AD, Stolte M, Ell C. Long term results of PDT for early neoplasia in Barrett’s esophagus. Gastrointest Endosc 2004;59:A257.
82. Peters F, Kara M, Rosmolen W, Aalders M, Ten Kate F, Krishnadath K, et al. Poor results of 5-aminolevulinic acid-photodynamic therapy for residual high-grade dysplasia and early cancer in barrett esophagus after endoscopic resection. Endoscopy 2005;37:418–24.
83. Peters F, Kara M, Rosmolen W, ten Kate F, Bultje B, Krishnadath S, et al. Endoscopic resection combined with photodynamic therapy for high grade dysplasia and early cancer in Barrett’s esophagus. Gastrointest Endosc 2004;59:A251.
84. Peters FP, Kara MA, Rosmolen WD, Aalders MCG, Ten Kate FJW, Bultje BC, et al. Endoscopic treatment of high-grade dysplasia and early stage cancer in Barrett’s esophagus. Gastrointest Endosc 2005;61:506–14.
85. Prasad GA, Wang KK, Buttar NS, Wongkeesong L-M, Krishnadath KK, Nichols FC, III, et al. Long-term survival following endoscopic and surgical treatment of high-grade dysplasia in Barrett’s esophagus. Gastroenterology 2007;132:1226–33.
86. Prasad GA, Wang KK, Buttar NS, Wongkeesong L-M, Lutzke LS, Borkenhagen LS. Predictors of stricture formation after photodynamic therapy for high-grade dysplasia in Barrett’s esophagus. Gastrointest Endosc 2007;65:60–6.
87. Rahmani EY, Rex DK, Ciaccia D, Turpin CS. Photodynamic therapy for ablation of esophageal high grade dysplasia and superficial cancer. Gastrointest Endosc 2000;51:3539.
88. Rahmani EY, Turpin C, Arney K. Photodynamic therapy for dysplastic Barrett’s esophagus and early esophageal adenocarcinoma should be first line therapy! Gastrointest Endosc 2004;59:A250.
89. Schembre DB, Huang JL, Lin OS, Cantone N, Low DE. Treatment of Barrett’s esophagus with early neoplasia: a comparison of endoscopic therapy and esophagectomy. Gastrointest Endosc 2008;67:595–601.
90. Schweitzer VG. Photodynamic therapy: 1994 treatment of benign and malignant upper aerodigestive tract disease. SPIE Proceedings Series 1995;2371:403–17.
91. Shah AK, Wolfsen HC, Hemminger LL, Shah AA, DeVault KR. Changes in esophageal motility after porfimer sodium photodynamic therapy for Barrett’s dysplasia and mucosal carcinoma. Dis Esophagus 2006;19:335–9.
92. Sylantiev C, Schoenfeld N, Mamet R, Groozman GB, Drory VE. Acute neuropathy mimicking porphyria induced by aminolevulinic acid during photodynamic therapy. Muscle Nerve 2005;31:390–3.
93. Triadafilopoulos G. Photodynamic therapy for the treatment of patients with Barrett’s high-grade dysplasia and mucosal adenocarcinoma. Nat Clin Pract Gastroenterol Hepatol 2005;2:136–7.
94. van Hillegersberg R, Haringsma J, ten Kate FJW, Tytgat GNJ, van Lanschot JJB. Invasive carcinoma after endoscopic ablative therapy for high-grade dysplasia in Barrett’s oesophagus. Dig Surg 2003;20:440–4.
95. Wang KK, Buttar NS, Lutzke LS, Anderson MA, Krisnadath K. Long-term results of photodynamic therapy for Barrett’s esophagus. Gastrointest Endosc 2000;51:4915.
96. Wang KK, Gutta K, Laukka MA. Phototherapy of Barrett’s esophagus. SPIE Proceedings Series 1994;2133:33–8.
97. Wang KK, Song L, Buttar N, Papenfuss S, Lutzke L. Barretts esophagus after photodynamic therapy: Risk of cancer development during long term follow-up. Gastroenterology 2004;126:A50.
98. Weiss A, Wiesinger H, Owen D. Photodynamic therapy of high grade dysplasia in Barrett’s esophagus: results from treatment of 17 patients. Gastrointest Endosc 2005;61:A145.
99. Weiss AA, Wiesinger HAR, Owen D. Photodynamic therapy in Barrett’s esophagus: results of treatment of 17 patients. Can J Gastroenterol 2006;20:261–4.
100. Wolfsen HC, Hemminger LI. Photodynamic therapy for dysplastic Barrett’s esophagus and mucosal adenocarcinoma. Gastrointest Endosc 2004;59:A251.
101. Wolfsen HC, Hemminger LL, Raimondo M, Woodward TA. Photodynamic therapy and endoscopic mucosal resection for Barrett’s dysplasia and early esophageal adenocarcinoma. South Med J 2004;97:827–30.
102. Wolfsen HC, Hemminger LL, Wallace MB, Devault KR. Clinical experience of patients undergoing photodynamic therapy for Barrett’s dysplasia or cancer. Aliment Pharmacol Ther 2004;20:1125–31.
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103. Wolfsen HC, Ng CS. Cutaneous consequences of photodynamic therapy. Cutis 2002;69:140–2.
104. Wolfsen HC, Woodward TA. Photofrin PDT for Barrett’s esophagus and early esophageal cancer. Recent Advances in Diseases of the Esophagus, 8th World Congress of the International Society for Diseases of the Esophagus, Sao Paulo, Brazil, 2001. pp. 149–53.
105. Wolfsen HC, Woodward TA, Raimondo M. Photodynamic therapy for dysplastic Barrett
esophagus and early esophageal adenocarcinoma. Mayo Clin Proc 2002;77:1176–81.
106. Yachimski P, Puricelli WP, Nishioka NS. Patient predictors of esophageal stricture development after photodynamic therapy. Clin Gastroenterol Hepatol 2008;6:302–8.
107. Zopf T, Rosenbaum A, Apel D, Jakobs R, Arnold JC, Riemann JF. [Photodynamic therapy of dysplasias and early carcinomas in Barrett esophagus with a diode laser system: a pilot study.] Med Klin 2001;96:212–16.
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One hundred and fifty publications, with study designs that did not meet the inclusion
criteria for the review, reported on patients with oesophageal cancer being treated with PDT. The references are listed below in alphabetical order; they have not been categorised and may still contain a number of duplicate publications.
References1. Anonymous. Photodynamic therapy effective for
swallowing problems. Oncology 1999;13:937.
2. Baconnier M, Phelip JM, Germain E, Durand A, Balosso J, Bichard P, et al. [External radiotherapy and photodynamic therapy for esophageal carcinoma: a dangerous association?] Gastroenterol Clin Biol 2008;32:221–3.
3. Bai XM, Shen GR, Chen WG, Guo T. Observation of curative effect photodynamic therapy for 42 cases of moderate or late stage in esophagus cancer. SPIE Proceedings Series 1998;3344:114–16.
4. Ban S, Mino M, Nishioka NS, Puricelli W, Zukerberg LR, Shimizu M, et al. Histopathologic aspects of photodynamic therapy for dysplasia and early adenocarcinoma arising in Barrett’s esophagus. Am J Surg Pathol 2004;28:1466–73.
5. Calzavara F, Tomio L. Photodynamic therapy: clinical experience at the Department of Radiotherapy at Padova General Hospital. J Photochem Photobiol B 1991;11:91–5.
6. Calzavara F, Tomio L, Corti L, Zorat PL, Barone I, Peracchia A, et al. Oesophageal cancer treated by photodynamic therapy alone or followed by radiation therapy. J Photochem Photobiol B 1990;6:167–74.
7. Calzavara F, Tomio L, Norberto L, Peracchia A, Corti L, Zorat PL, et al. Photodynamic therapy in the treatment of malignant tumours of the upper aerodigestive tract. Lasers Med Sci 1989;4:279–84.
8. Chissov VI, Sokolov VV, Trakhtenberg AK, Mamontov AS. Photodynamic therapy of early stage cancer of lung, esophagus, and stomach with two different photosensitizers. SPIE Proceedings Series 1995;2625:466–75.
9. Corti L, Noverto L, Belfontali S, Schaffer M. Long survival-rate in patients with esophagus cancer treated with PDT. In Waidelich W, Waidelich R, Hofstetter A, editors. Lasers in medicine. Munich, Germany: Springer-Verlag; 1993. pp. 268–71.
10. Corti L, Skarlatos J, Boso C, Cardin F, Kosma L, Koukourakis MI, et al. Outcome of patients receiving photodynamic therapy for early esophageal cancer. Int J Radiat Oncol Biol Phys 2000;47:419–24.
11. Craig C, Gray J, Macpherson M, Hodgson H, Zammit M, Fullarton G. Porfimer sodium photodynamic therapy in the treatment of early oesophageal carcinoma. Photodiag Photodyn Ther 2007;4:244–8.
12. Craig C, Macpherson M, Hodgson H, Gray J, Zammit M, Fullarton G. Photodynamic therapy of early oesophageal carcinoma. Gut 2006;55:76.
13. Craig CF, MacPherson M, Hodgson H, Gray J, Zammit M, Fullarton G. Photodynamic therapy is of benefit in treatment of early oesophageal carcinoma. Gastroenterology 2006;130:A414.
14. Dal Fante M, Lombardo L, Conio M, Mancini A, Spinelli P. [Photodynamic therapy of the superficial esophageal carcinoma in Barrett’s esophagus.] Giorn Ital Endosc Digest 1995;18:171–6.
15. Eickhoff A, Jakobs R, Weickert U, Hartmann D, Schilling D, Alsenbesy M, et al. Long-segment early squamous cell carcinoma of the proximal esophagus: curative treatment and long-term follow-up after 5-aminolevulinic acid (5-ALA)-photodynamic therapy. Endoscopy 2006;38:641–3.
16. Etienne J, Canard JM. [Photodynamic therapy in liberal practice.] Acta Endoscopica 2007;37:397–8.
17. Everette SS, Sethi A, DeCosta GB, Zfass AM. A 10 year, single center experience with PDT in esophageal lesions. Am J Gastroenterol 2006;101:94.
18. Fujimaki M, Nakayama K. Endoscopic laser treatment of superficial esophageal cancer. Semin Surg Oncol 1986;2:248–56.
19. Go JT, Dumot JA, Lopez R, Vargo J, Zuccaro G, Falk G, et al. Photodynamic therapy in Barrett’s esophagus with high grade dysplasia and intra-mucosal carcinoma. Am J Gastroenterol 2006;101:66.
Appendix 8 Oesophageal cancer scoping
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20. Goodell TT, Jacques SL, Gregory KW, Dougherty TJ. Evaluating clinical outcomes of PDT. SPIE Proceedings Series 2001;4248:1–9.
21. Gossner L, May A, Sroka R, Stolte M, Hahn EG, Ell C. Photodynamic destruction of high grade dysplasia and early carcinoma of the esophagus after the oral administration of 5-aminolevulinic acid. Cancer 1999;86:1921–8.
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One hundred and seventy-seven publications, with study designs that did not meet the
inclusion criteria for the review, reported on patients with lung cancer being treated with PDT. Details are lacking for many of these publications, so the categorisations may not be reliable.
There are 10 observational comparative studies, with sample sizes ranging from 29 to 687, although the sample size is unclear for one-half of them.1–10 For some of these studies, all of the patients receive PDT, for others it is series of patients undergoing treatment for lung cancer, only a proportion of which receive PDT.
Eleven publications are described as trials but without a comparator group (Phase I/II/pilot studies), with sample sizes ranging from 9 to 54.11–21
One hundred and nineteen publications report case series;22–140 19 have over 100 patients, eight publications report on case series with between 50 and 100 patients, and 71 report less than 50 patients. For 21 publications it is not clear what the sample size is. Many of these publications are by the same authors and appear to be updated series of patients or duplicate reports published in different journals. Therefore, these publications may double count patients to a certain degree.
Thirty publications report less than 10 patients,141–170 16 of which are single case reports.142,143,146,147,149,151,152,155–157,161,163,164,166,167,169
A further seven publications remain uncategorised (e.g. the paper is unavailable, it is unclear what is being reported, or possible duplicate publication).171–177
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134. Usuda J, Tsutsui H, Honda H, Ichinose S, Ishizumi T, Hirata T, et al. Photodynamic therapy for lung cancers based on novel photodynamic diagnosis using talaporfin sodium (NPe6) and autofluorescence bronchoscopy. Lung Cancer 2007;58:317–23.
135. Vakoulovskaia E, Chental V, Kuvshinov Y, Poddubny B, Ivanov AV, Kazaryan MA. New approaches to photodynamic therapy of tumors with Al phtalocyanine. SPIE Proceedings Series 2000;4059:32–8.
136. Vandenbergh H. Photodynamic therapy and photodetection of early cancer in the upper aerodigestive tract, the tracheobronchial tree, the oesophagus and the urinary bladder. Hadron Ther Oncol 1994;1077:577–621.
137. Vincent RG, Dougherty TJ, Rao U, Boyle DG, Potter WR. Photoradiation therapy in advanced carcinoma of the trachea and bronchus. Chest 1984;85:29–33.
138. Wile AG, Coffey J, Nahabedian MY, Baghdassarian R, Mason GR, Berns MW. Laser photoradiation therapy of cancer: an update of the experience at the University of California, Irvine. Lasers Surg Med 1984;4:5–12.
139. Yamamoto H, Kato H, Okunaka T, Eckhauser ML, Bonaminio A, Konaka C, et al. Photodynamic therapy with the excimer dye laser in the treatment of respiratory tract malignancies. Laser Life Sci 1991;4:125–33.
140. Yoon SH, Han KT, Kim GN, Lee SI. [Effect of photodynamic therapy in lung cancer.] Chin J Tuberc Respir Dis 2004;57:358–63.
Case reports (single case or fewer than 10 patients)141. Andouin H, Patrice T, Foultier MT, Courtin V,
Dabouis G. HpD-PDT for cancer treatment in bronchology. Chest 1987;92:767–8.
142. DeArmond DT, Mahtabifard A, Fuller CB, McKenna RJ, Jr. Photodynamic therapy followed by thoracoscopic sleeve lobectomy for locally advanced lung cancer. Ann Thorac Surg 2008;85:e24–6.
143. Downie GH, Cuenca RE, Allison RR, McIlroy BW. A comparison of interstitial and superficial light delivery for photodynamic therapy of intraluminal neoplasms. J Bronchol 2002;9:193–6.
144. Downie GH, Qureshi A, Loewen G, Cuenca R, Allison R, Sibata C. Endobronchial ablation of typical carcinoid tumor with photodynamic therapy. J Bronchol 2007;14:10–14.
145. Feintrenie X, Lignon D, Arboit F, Menard O, Jonveaux E, Martinet Y, et al. [Experience of photodynamic therapy in inoperable bronchogenic cancer in the city of Nancy. Apropos of 3 cases.] Rev Pneumol Clin 1992;48:129–30.
146. Gamarra F, Baumgartner R, Stepp H, Rick K, Leberig A, Huber RM. 5-aminolaevulinic acid for fluorescence diagnosis and photodynamic therapy of bronchial cancer – a case report. SPIE 1995;2371:398–402.
147. Haussinger K, Huber RM, Krug M, Baumgartner R, Stepp H, Unsold E, et al. Bronchoscopic photodynamic therapy of bronchial carcinoma. Endoscopy 1989;21:285–8.
148. Haussinger K, Huber RM, Krug M, Breyer G, Baumgartner R, Beyer W, et al. [Photodynamic therapy of bronchial cancer.] Pneumologie 1990;44:687–93.
149. Horai T, Nakamura SI, Nishio H, Sakuma T, Ikegami H, Matsuda M. A five-year disease-free survivor of multiple unresectable lung cancer treated by photoradiation therapy with haematoporphyrin derivative. Lasers Med Sci 1989;4:1–5.
150. Jang TW, Kim HK, Oak CH, Jung MH. Photodynamic therapy in early lung cancer: a report of two cases. Korean J Intern Med 2006;21:178–82.
151. Kato H, Konaka C, Kawate N, Shinohara H, Kinoshita K, Noguchi M, et al. Five-year disease-free survival of a lung cancer patient treated only by photodynamic therapy. Chest 1986;90:768–70.
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152. Kato H, Konaka C, Okunaka T, Nakamura H, Taguchi M, Masada S, et al. Ten year disease-free survival of a lung cancer patient treated only by photodynamic therapy (PDT). Laser Life Sci 1994;6:9–14.
153. Kim YK, Lee YM, Kim KU, Uh ST, Kim YH, Park CS. [Clinical experience of photodynamic therapy in five patients with advanced lung cancer.] Tuberc Respir Dis 2004;57:72–7.
154. Konaka C, Kato H, Hayata Y. Lung cancer treated by photodynamic therapy alone: survival for more than three years. Lasers Med Sci 1987;2:17–19.
155. Kondo K, Miyoshi T, Takizawa H, Kenzaki K, Sakiyama S, Tangoku A. Photodynamic therapy for submucosal tumor of the central bronchus. J Med Invest 2005;52:208–11.
156. Kseibi SA, Childs CJ, Allison RR, Cuenca RE, Downie GH. Interventional endoscopic modalities for primary tracheal malignancy: Photodynamic therapy and temporary stenting. Chest 2003;124:291S.
157. Kubota K, Furuse K, Kawaguchi T, Kawahara M, Ogawara M, Yamamoto S. A case of long-term survival with stage IV small cell lung cancer and early-stage central-type squamous cell lung cancer treated by photodynamic therapy. Jpn J Clin Oncol 1999;29:45–8.
158. McCaughan FM, Janes SM, Read CA, Mosse CA, Bown S, George PJ. Photodynamic therapy in the treatment of early stage lung cancer: internal report to the Use of Medicines Committee [unpublished]. London: University College Hospital; 2009.
159. McCaughan JS, Jr. Photoradiation of malignant tumors presensitized with hematoporphyrin derivative. Prog Clin Biol Res 1984;170:805–27.
160. McCaughan JS, Jr, Guy JT, Hawley P, Hicks W, Inglis W, Laufman L, et al. Hematoporphyrin-derivative and photoradiation therapy of malignant tumors. Lasers Surg Med 1983;3:199–209.
161. Moghissi K, Dixon K. Photodynamic therapy for synchronous occult bronchial cancer 17 years after pneumonectomy. Interact Cardiovasc Thorac Surg 2005;4:327–8.
162. Moghissi K, Parsons RJ, Dixon K. Photodynamic therapy (PDT) for bronchial carcinoma with the use of rigid bronchoscope. Lasers Med Sci 1992;7:381–5.
163. Mortman KD, Frankel KM. Pulmonary resection after successful downstaging with photodynamic therapy. Ann Thorac Surg 2006;82:722–4.
164. Nelson JS, Fairshter RD, Berns MW. Long-term survival of a lung cancer patient treated with photodynamic therapy. Lasers Surg Med 1990;10:208–10.
165. Okunaka T, Kato H, Konaka C, Furukawa K, Harada M, Yamamoto Y. Photodynamic therapy of lung cancer with bronchial artery infusion of photofrin. Diagn Ther Endosc 1996;2:203–6.
166. Saito M, Kato H, Konaka C, Okunaka T, Furukawa K, Sakai H, et al. Synchronous quadruple lung cancer treated curatively by photodynamic therapy. Diagn Ther Endosc 1996;3:115–19.
167. Saito M, Wei BR, Furukawa K, Konaka C, Kato H, Ebihara Y. [A case of squamous cell carcinoma of the lung treated by right sleeve upper lobectomy after photodynamic therapy.] Nippon Kyobu Geka Gakkai 1992;40:1788–91.
168. Shimatani H, Okunaka T, Shibuya H, Furukawa T, Ikeda N, Konaka C, et al. [Preoperative PDT for early stage lung cancer accompanied with infiltration to the central airway.] Kyobu Geka 2001;54:957–61.
169. Sutedja T, Kwa B, van Kamp H, van Zandwijk N. Photodynamic therapy as an alternative treatment for surgery in a patient with lung cancer undergoing bone marrow transplantation. Chest 1993;103:1908–9.
170. Takehara N, Ohsaki Y, Fujiuchi S, Yamaguchi S, Akiba Y, Nakano H, et al. [Effects of photodynamic therapy in inoperable early stage lung cancer patients.] Jpn J Lung Cancer 1995;35:127–32.
Uncategorised171. Downie G, Qureshi A, Childs C, Ron A, Claudio
S, Rosa C, et al. Endobronchial ablation of typical carcinoid tumor with photodynamic therapy. Lung Cancer 2005;49:S155-S6.
172. Isaev VM, Zenger VG, Musatenko LI, Nasedkin AN, Petlev AA. [Updated laser technologies in otorhinolaryngology.] Vestn Otorinolaringol 2001;5:33–5.
173. Li PS. [Photoradiation treatment of broncho-pulmonary carcinoma with hematoporphyrin derivative and microwaves through broncho-fiberscopy.] Chung Hua Chieh Ho Ho Hu Hsi 1986;9:98–9.
174. Loewen GM, Pandey R, Bellnier D, Henderson B, Dougherty T. Endobronchial photodynamic therapy for lung cancer. Lasers Surg Med 2006;38:364–70.
175. Mantareva V, Kassabov K, Shopova M, Mueller S. Influence of photodynamic therapy on the delay of
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metastasis development in Lewis lung carcinoma. SPIE 1994;2325:355–63.
176. Sanfilippo NJ, Hsi A, DeNittis AS, Ginsberg GG, Kochman ML, Friedberg JS, et al. Toxicity of photodynamic therapy after combined external beam radiotherapy and intraluminal brachytherapy
for carcinoma of the upper aerodigestive tract. Lasers Surg Med 2001;28:278–81.
177. Sutedja G, Risse R, Van Mourik JC, Postmus PE. Photodynamic therapy for treatment of bronchial carcinomas. Thorax 1994;49:289–90.
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Thirty publications, with study designs that did not meet the inclusion criteria for the review
reported on patients with biliary tract cancer being treated with PDT. Details are lacking for many of these publications, so the categorisations may not be reliable.
There is one comparative study, which is published in Korean;1 the information is taken from the English abstract, which provides no methodological details. This study, of patients with advanced hilar cholangiocarcinoma, is a retrospective analysis of 27 patients who were treated with PDT under percutaneous cholangioscopy plus additional percutaneous biliary drainage compared with 20 patients who were treated with endoscopic biliary drainage alone.
Twelve publications are described as trials but without a comparator group (Phase I/II/pilot studies), with sample sizes ranging from 1 to 44.2–13 One of these, a Phase II trial of 24 patients with Bismuth III/IV cholangiocarcioma treated with PDT after sensitization with Ps, also reports a retrospective comparison with a historical control group of 20 patients who fulfilled the inclusion criteria for the prospective study.4
Seven publications report case series with at least 10 patients but all of them have less than 50 patients.14–20 Ten publications report fewer than 10 patients,21–30 three of which are single case reports.21–23
ReferencesObservational comparative studies1. Cheon YK, Cho YD, Baek SH, Cha SW, Moon JH,
Kim YS, et al. [Comparison of survival of advanced hilar cholangiocarcinoma after biliary drainage alone versus photodynamic therapy with external drainage][see comment.] Korean J Gastroenterol 2004;44:280–7.
Experimental non-comparative studies2. Berr F, Tannapfel A, Lamesch P, Wiedmann M.
Endoscopic palliation of bile duct cancer with photodynamic therapy. Hepatology 1997;26:200.
3. Berr F, Wiedmann M, Tannapfel A, Halm U, Kohlhaw KR, Schmidt F, et al. Photodynamic
therapy for advanced bile duct cancer: evidence for improved palliation and extended survival. Hepatology 2000;31:291–8.
4. Dumoulin FL, Gerhardt T, Fuchs S, Scheurlen C, Neubrand M, Layer G, et al. Phase II study of photodynamic therapy and metal stent as palliative treatment for nonresectable hilar cholangiocarcinoma. Gastrointest Endosc 2003;57:860–7.
5. Harewood GC, Baron TH, Rumalla A, Wang KK, Gores GJ, Stadheim LM, et al. Pilot study to assess patient outcomes following endoscopic application of photodynamic therapy for advanced cholangiocarcinoma. J Gastroenterol Hepatol 2005;20:415–20.
6. Kaya M, de Groen PC, Angulo P, Nagorney DM, Gunderson LL, Gores GJ, et al. Treatment of cholangiocarcinoma complicating primary sclerosing cholangitis: the Mayo Clinic experience. Am J Gastroenterol 2001;96:1164–9.
7. Ortner MA, Liebetruth J, Mansmann U, Voderholzer W, Michetti P, Schachschal G, et al. Photodynamic therapy of malignant bile duct tumors. Gastroenterology 2003;124:A565.
8. Pereira SP, Aithal G, Devlin J, Meadows HM. Photostent 1: a phase II trial of porfimer sodium photodynamic therapy in locally advanced biliary tract carcinoma. Gut 2006;55:A116.
9. Pereira SP, Ayaru L, Rogowska A, Mosse A, Hatfield ARW, Bown SG. Photodynamic therapy of malignant biliary strictures using meso-tetrahydroxyphenylchlorin. Eur J Gastroenterol Hepatol 2007;19:479–85.
10. Pereira SP, Ragunath K, Devlin J, Meadows HM. Preliminary results of a phase II trial to examine the safety and efficacy of porfimer sodium photodynamic therapy (PDT) in locally advanced biliary tract carcinoma (BTC). J Clin Oncol 2005;23:A4180.
11. Wiedmann M, Berr F, Schiefke I, Witzigmann H, Kohlhaw K, Mossner J, et al. Photodynamic therapy in patients with non-resectable hilar cholangiocarcinoma: 5-year follow-up of a prospective phase II study. Gastrointest Endosc 2004;60:68–75.
Appendix 10 Biliary tract cancer scoping
Appendix 10
176
12. Wiedmann M, Caca K, Berr F, Schiefke I, Tannapfel A, Wittekind C, et al. Neoadjuvant photodynamic therapy as a new approach to treating hilar cholangiocarcinoma: a phase II pilot study. Cancer 2003;97:2783–90.
13. Wolkersdorfer G, Emmanuel K, Denzer U, Puespoek A, Neureiter D, Kiesslich T, et al. P-150 Temoporfin improves tumoricidal efficacy of photodynamic therapy (PDT) for bile duct cancer. International Liver Cancer Association Annual Conference, Chicago, 2008. p. 60.
Case series (10 or more patients)14. Abulafi AM, Allardice JT, Williams NS, van Someren
N, Swain CP, Ainley C. Photodynamic therapy for malignant tumours of the ampulla of Vater. Gut 1995;36:853–6.
15. Itoi T, Sofuni A, Itokawa F, Shinohara Y, Takeda K, Nakamura K, et al. Salvage therapy in patients with unresectable hilar cholangiocarcinoma. Digestive Endoscopy 2006;18:232–8.
16. Maunoury V, Mordon S, Boyer J, Quentin V, Barthet M, Laugier R, et al. Results of a multicenter open study of photodynamic therapy (Photofrin) in 49 patients with cholangiocarcinoma. Photodynamic Therapy and Photodiagnosis in Clinical Practice, Brixen/Bressanone, 7–11 October 2008.
17. Ortner M. Photodynamic therapy for cholangiocarcinoma. J Hepatobiliary Pancreat Surg 2001;8:137–9.
18. Prasad GA, Wang KK, Baron TH, Buttar NS, Wongkeesong L-M, Roberts LR, et al. Factors associated with increased survival after photodynamic therapy for cholangiocarcinoma. Clin Gastroenterol Hepatol 2007;5:743–8.
19. Shim CS, Cheon YK, Cha SW, Bhandari S, Kim YS, Cho YD, et al. Percutaneous transhepatic photodynamic therapy for advanced bile duct cancer and role of intraductal ultrasonography (IDUS) in the follow-up and response assessment. Gastrointest Endosc 2003;57:A199.
20. Shim CS, Cheon YK, Cha SW, Bhandari S, Moon JH, Cho YD, et al. Prospective study of the effectiveness of percutaneous transhepatic photodynamic therapy for advanced bile duct cancer and the role of intraductal ultrasonography in response assessment. Endoscopy 2005;37:425–33.
Case reports (single case or fewer than 10 patients)21. Berr F, Tannapfel A, Lamesch P, Pahernik S,
Wiedmann M, Halm U, et al. Neoadjuvant photodynamic therapy before curative resection of proximal bile duct carcinoma. J Hepatol 2000;32:352–7.
22. Burdick JS, Magee D, Miller G, Wright KB. Biliary photodynamic therapy alternative delivery technique. Endoscopy 2000;32:S63.
23. McCaughan JS, Jr, Mertens BF, Cho C, Barabash RD, Payton HW. Photodynamic therapy to treat tumors of the extrahepatic biliary ducts. A case report. Arch Surg 1991;126:111–13.
24. Nanashima A, Yamaguchi H, Shibasaki S, Ide N, Sawai T, Tsuji T, et al. Adjuvant photodynamic therapy for bile duct carcinoma after surgery: a preliminary study. J Gastroenterol 2004;39:1095–101.
25. Ortner MA, Liebetruth J, Schreiber S, Hanft M, Wruck U, Fusco V, et al. Photodynamic therapy of nonresectable cholangiocarcinoma. Gastroenterology 1998;114:536–42.
26. Rumalla A, Baron TH, Wang KK, Gores GJ, Stadheim LM, de Groen PC. Endoscopic application of photodynamic therapy for cholangiocarcinoma. Gastrointest Endosc 2001;53:500–4.
27. Suzuki S, Inaba K, Yokoi Y, Ohata K, Ota S, Azuma M, et al. Photodynamic therapy for malignant biliary obstruction: a case series. Endoscopy 2004;36:83–7.
28. Zoepf T, Jakobs R, Arnold JC, Apel D, Rosenbaum A, Riemann JF. Photodynamic therapy for palliation of nonresectable bile duct cancer – preliminary results with a new diode laser system. Am J Gastroenterol 2001;96:2093–7.
29. Zoepf T, Jakobs R, Rosenbaum A, Apel D, Arnold JC, Riemann JF. Photodynamic therapy with 5-aminolevulinic acid is not effective in bile duct cancer. Gastrointest Endosc 2001;54:763–6.
30. Zoepf T, Jakobs R, Arnold JC, Apel D. Photodynamic therapy (PDT) for palliation of non resectable bile duct cancer: first results with a new diode laser system. Gastroenterology 1999;116:G2357.
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Forty-three publications, with study designs that did not meet the inclusion criteria for
the review, reported on patients with brain cancer being treated with PDT. Details are lacking for many of these publications, so the categorisations may not be reliable.
There are two studies with some form of comparison group, but both studies are poorly reported and lack methodological details.1–2
One comparative study reports the results of a Phase II trial of PDD/PDT in 26 patients with WHO grade IV recurrent glioblastoma who were sensitised with mTHPC (FOSCAN) prior to fluorescent guided resection and intraoperative PDT after 4 days.2 This group of patients was compared with a control group of matched patients, but no details of how they were matched are provided.
The other comparative study reported on 30 patients [27 glioma (nine of which were recurrences), two malignant meningioma, two metastatic brain cancer] treated with high-dose PDT (haematoporphyrin derivative and pumped dye laser) in addition to craniotomy with a radical or partial excision of the tumour.1 The authors state that 30 comparable patients who were treated with surgery alone were selected at random as control subjects, but no details are provided so it is not clear how these patients were selected.
Thirteen publications are described as being trials but without a comparator group, the number of patients ranging from 3 to 186.3–15 Some of the publications appear to be related, either potential duplicate publications or reporting different outcomes for the same patients.
Twenty-two publications report case series with at least 10 patients16–37 and six publications report less than 10 patients,38–43 two of which are single case reports.38–43 Of the 22 publications, four had between 50 and 100 patients,26,27,29,30 and only three had more than 100 patients (one of which included various treatments and so not all patients will have undergone PDT).32,33,35
Many of the publications appear to be from the same clinical groups (14 are authored by Muller et al. and six by Kostron et al.) and there may well be significant overlap in the results presented (updating as more patients have been treated). Muller et al. began two RCTs that were not completed (see Chapter 11, Stopped trials) and some of the publications authored by them appear to report characteristics of the cohort of trial patients, but not comparative results.
ReferencesObservational comparative studies1. Chen ZQ, Wu S, Zhu SG. Adjuvant photodynamic
therapy in surgical management of cerebral tumors. SPIE 1993;1616:94–7.
2. Kostron H, Fiegele T, Akatuna E. Combination of FOSCAN mediated fluorescence guided resection and photodynamic treatment as new therapeutic concept for malignant brain tumors. Med Laser Appl 2006;21:285–90.
Experimental non-comparative studies3. Fedulov AS, Sakovich II, Sliakhtsin SV, Trukhachova
TV. PDT of high-grade gliomas with Fotolon. Results of an open-label randomized clinical trial. Photodiagn Photodyn Ther 2008;5(Suppl. 1):S7.
4. Kostron H, Fritsch E, Grunert V. Photodynamic therapy of malignant brain tumours: a phase I/II trial. Br J Neurosurg 1988;2:241–8.
5. Laws ER, Jr, Cortese DA, Kinsey JH, Eagan RT, Anderson RE. Photoradiation therapy in the treatment of malignant brain tumors: a phase I (feasibility) study. Neurosurgery 1981;9:672–8.
6. Marks PV, Belchetz PE, Saxena A, Igbaseimokumo U, Thomson S, Nelson M, et al. Effect of photodynamic therapy on recurrent pituitary adenomas: clinical phase I/II trial: an early report. Br J Neurosurg 2000;14:317–25.
7. Muller P, Wilson B, Dougherty TJ. Photodynamic therapy of supratentorial gliomas. SPIE 1997;2972:14–26.
8. Muller P, Wilson B, Lilge L, Hitchcock M, Hertzel F, Chen Q, et al. Photodynamic therapy of malignant brain tumors: results from a Phase II trial and
Appendix 11 Brain cancer scoping
Appendix 11
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demographics from a Phase III trial [Abstract.] Can J Neurol Sci 1999;26:S31.
9. Muller P, Wilson B, Lilge L, Varma S, Bogaards A, Fullagar, et al. Clinical studies of photodynamic therapy for malignant brain tumors: facial nerve palsy after temporal fossa photoillumination. SPIE 2003;4952:97–103.
10. Muller P, Wilson B, Lilge L, Yang V, Hetzel, Chen Q, et al. Photofrin: Photodynamic therapy for malignant brain tumors. SPIE 2001;4248:34–45.
11. Muller P, Wilson B, Lilge L, Yang V, Hitchcock M, Hetzel F, et al. Clinical trials of photodynamic therapy of malignant brain tumors. SPIE 2000;3909:10–19.
12. Muller P, Wilson B, Lilge L, Yang V, Varma A, Bogaars A, et al. Clinical studies of photodynamic therapy for malignant brain tumors: Karnofsky score and neurological score in patients with recurrent gloms treated with Photofrin-PDT. SPIE 2002;4612:40–7.
13. Origitano TC, Reichman OH. Photodynamic therapy for intracranial neoplasms: development of an image-based computer-assisted protocol for photodynamic therapy of intracranial neoplasms. Neurosurgery 1993;32:587–95, discussion 95–96.
14. Rosenthal MA, Kavar B, Uren S, Kaye AH. Promising survival in patients with high-grade gliomas following therapy with a novel boronated porphyrin. J Clin Neurosci 2003;10:425–7.
15. Varma AK, Muller PJ. Cranial neuropathies after intracranial Photofrin-photodynamic therapy for malignant supratentorial gliomas: a report on 3 cases. Surg Neurol 2008;70:190–3.
Case series (10 or more patients)16. Beck TJ, Kreth FW, Beyer W, Mehrkens JH,
Obermeier A, Stepp H, et al. Interstitial photodynamic therapy of nonresectable malignant glioma recurrences using 5-aminolevulinic acid induced protoporphyrin IX. Lasers Surg Med 2007;39:386–93.
17. Chen L-f, Ke Y-q, Yang Z-l, Wang S-q, Xu R-x. [Effect of photodynamic therapy combined with interstitial chemotherapy for gliomas.] Di Yi Jun Yi Da Xue Xue Bao 2005;25:116–18.
18. Kaneko S. Clinical results of stereotactic intratumoral photodynamic therapy for malignant brain tumors. Clin Lasers Diagn 2000;1:222–30.
19. Kaye AH, Morstyn G, Brownbill D. Adjuvant high-dose photoradiation therapy in the treatment of cerebral glioma: a phase 1–2 study. J Neurosurg 1987;67:500–5.
20. Kostron H, Grunert V. [Photodynamic therapy of malignant brain tumors.] Wien Klin Wochenschr 1987;99:389–92.
21. Kostron H, Obwegeser A, Jakober R, Zimmermann A, Rueck A, Dougherty TJ. Experimental and clinical results of mTHPC (Foscan R)-mediated photodynamic therapy for malignant brain tumors. SPIE 1998;3247:40–5.
22. Kostron H, Plangger C, Fritsch E, Maier H. Photodynamic treatment of malignant brain tumors. Wien Klin Wochenschr 1990;102:531–5.
23. Kostron H, Weiser G, Fritsch E, Grunert V. Photodynamic therapy of malignant brain tumors: clinical and neuropathological results. Photochem Photobiol 1987;46:937–43.
24. McCulloch GA, Forbes IJ, See KL, Cowled PA, Jacka FJ, Ward AD. Phototherapy in malignant brain tumors. Prog Clin Biol Res 1984;170:709–17.
25. Mehrkens J, Stummer W, Beck T, Tonn J, Kreth F. Interstitial photodynamic therapy of recurrent malignant gliomas using 5-aminolevulinic acid (5-ALA). Neuro Oncol 2005;7:110.
26. Muller P, Wilson B. Photodynamic therapy of malignant brain-tumors – supplementary postoperative light delivery by implanted optical fibers: field fractionation. SPIE 1991;1426:254–65.
27. Muller P, Wilson B, Dougherty TJ. Photodynamic therapy of supratentorial gliomas. SPIE 1998;3247:2–13.
28. Muller PJ, Wilson BC. Photodynamic therapy of malignant primary brain tumours: clinical effects, post-operative ICP, and light penetration of the brain. Photochem Photobiol 1987;46:929–35.
29. Muller PJ, Wilson BC. Photodynamic therapy of malignant brain tumours. Can J Neurol Sci 1990;17:193–8.
30. Muller PJ, Wilson BC. Photodynamic therapy for recurrent supratentorial gliomas. Semin Surg Oncol 1995;11:346–54.
31. Muller PJ, Wilson BC. Photodynamic therapy for malignant newly diagnosed supratentorial gliomas. J Clin Laser Med Surg 1996;14:263–70.
32. Muller PJ, Wilson BC. Photodynamic therapy of brain tumors: a work in progress. Lasers Surg Med 2006;38:384–9.
33. Obwegeser A, Ortler M, Seiwald M, Ulmer H, Kostron H. Therapy of glioblastoma multiforme: a cumulative experience of 10 years. Acta Neurochir 1995;137:29–33.
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34. Schmidt MH, Meyer GA, Reichert KW, Cheng J, Krouwer HG, Ozker K, et al. Evaluation of photodynamic therapy near functional brain tissue in patients with recurrent brain tumors. J Neurooncol 2004;67:201–7.
35. Stylli SS, Kaye AH, MacGregor L, Howes M, Rajendra P. Photodynamic therapy of high grade gliom: long term survival. J Clin Neurosci 2005;12:389–98.
36. Zhu SG. [Application of adjuvant photodynamic therapy in the treatment of malignant brain tumors.] Chin J Clin Oncol 1993;20:894–6.
37. Zhu SG, Wu S, Chen ZQ, Sun W. Photodynamic therapy of recurrent cerebral glioma. SPIE 1993;1616:115–18.
Case reports (single case or fewer than 10 patients)38. Benzer A, Putensen C, Kostron H. Photodynamic
therapy. Lancet 1989;2:382–3.
39. Kaneko S. [Photoradiation therapy (PRT). 7. Clinical study of photoradiation therapy: clinical
application and efficacy. d. Brain neoplasms.] Nippon Rinsho 1987;45:817–25.
40. Muller PJ, Wilson BC. Photodynamic therapy: cavitary photoillumination of malignant cerebral tumours using a laser coupled inflatable balloon. Can J Neurol Sci 1985;12:371–3.
41. Perria C, Carai M, Falzoi A, Orunesu G, Rocca A, Massarelli G, et al. Photodynamic therapy of malignant brain tumors: clinical results of, difficulties with, questions about, and future prospects for the neurosurgical applications. Neurosurgery 1988;23:557–63.
42. Powers SK, Cush SS, Walstad DL, Kwock L. Stereotactic intratumoral photodynamic therapy for recurrent malignant brain tumors. Neurosurgery 1991;29:688–95; discussion 95–96.
43. Stummer W, Beck T, Beyer W, Mehrkens JH, Obermeier A, Etminan N, et al. Long-sustaining response in a patient with non-resectable, distant recurrence of glioblastoma multiforme treated by interstitial photodynamic therapy using 5-ALA: case report. J Neurooncol 2008;87:103–9.
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One hundred and twenty-nine publications, with study designs that did not meet the
inclusion criteria for the review, reported on patients with head and neck cancer being treated with PDT. Details are lacking for many of these publications, so the categorisations may not be reliable.
There are three studies that appear to be comparative, although the precise design is not clear for any of them.1–3
Fifteen publications are described as trials but without a comparator group (Phase I/II pilot studies), with sample sizes ranging from 5 to 121.4–18
Eighty-seven publications report case series;19–105 eight have over 100 patients,26–28,33,61,87,94,105 but not all of these contain patients with only head and neck cancer; some studies report multiple cancer site series. Eleven publications report on case series, with between 50 and 100 patients, and 56 report less than 50 patients. For 12 publications it is not clear what the sample size is.19,39,40,48,56,57,6
0,64,68,82,85,99 Many of these publications are by the same authors and appear to be updated series of patients, or duplicate reports published in different journals. Therefore, these publications may double count patients to a certain degree.
Nineteen publications report fewer than 10 patients,106–124 seven of which are single case reports.108,110,112,115,120,121,124
A further five publications remain uncategorised.125–129
ReferencesObservational comparative studies1. Inoue H. [Voice evaluation after photodynamic
therapy for laryngeal cancer.] Otolaryngol Head Neck Surg 1997;69:407–10.
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Appendix 13 Actinic keratosis data extraction
Appendix 13
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189Stud
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n-in
filtr
atin
g A
K le
sion
s (u
p to
four
lesi
ons)
. Ext
ensi
ve
excl
usio
n cr
iteri
a w
ere
repo
rted
Pati
ent
char
acte
rist
ics
% M
ale:
56, a
ge n
ot
repo
rted
. The
maj
ority
of
patie
nts
had
thre
e or
few
er
lesi
ons;
mos
t w
ere
loca
ted
on t
he fa
ce/s
calp
and
wer
e th
in o
r m
oder
atel
y th
ick
Con
com
itan
t tr
eatm
ent
Not
sta
ted
Tria
l tre
atm
ents
MA
L–PD
T c
ompa
ring
in
cuba
tion
time
(1 h
r or
3 h
r) a
nd d
ose
(160
mg/
g or
80
mg/
g)In
terv
enti
on M
AL–
PDT
(1
hr +
160
mg/
g). M
ost
lesi
ons
wer
e pr
epar
ed u
sing
der
mal
cur
ette
to
rem
ove
scal
es a
nd c
rust
s. 1-
mm
-thi
ck la
yer
of
MA
L cr
eam
app
lied
to e
ach
lesi
on a
nd
to 5
mm
of s
urro
undi
ng a
rea.
Lesi
ons
cove
red
with
occ
lusi
ve d
ress
ing
for
spec
ified
incu
batio
n pe
riod
the
n w
iped
of
f with
sal
ine.
Les
ions
wer
e ill
umin
ated
w
ith r
ed la
mp
light
(w
avel
engt
h 57
0–67
0 nm
, int
ensi
ty 7
0 –
190
mW
/cm
2 )
to p
rovi
de t
otal
ligh
t do
se o
f 75
J/cm
2 . T
he m
ean
illum
inat
ion
time
was
aro
und
9.5
min
. Any
lesi
ons
with
out
CR
at
2 or
3
mth
wer
e gi
ven
2nd
PDT
tre
atm
ent.
Any
non
-CR
at
6 m
th o
ffere
d al
tern
ativ
e tr
eatm
ent
Com
para
tor
MA
L–PD
T
(3 h
r + 1
60 m
g/g)
as
abov
e2n
d co
mpa
rato
r M
AL–
PDT
(1
hr +
80
mg/
g) a
s ab
ove
3rd
com
para
tor
MA
L–PD
T
(3 h
r + 8
0 m
g/g)
as
abov
e
Mor
bidi
ty L
esio
n re
spon
se (
base
d on
11
0 pa
tient
s w
ith 3
80 le
sion
s, tw
o pa
tient
s w
ith fo
ur le
sion
s ex
clud
ed d
ue t
o w
rong
di
agno
sis)
. Ove
rall
lesi
on r
espo
nse
(not
cl
ear
if C
R)
85%
3 h
r + 1
60 m
g/g
76%
1
hr +
160
mg/
g 74
% 3
hr +
80
mg/
g 77
%
1 hr
+ 8
0 m
g/g.
Not
e: A
bout
one
-thi
rd o
f le
sion
s w
ere
not
debr
ided
as
per
prot
ocol
. Fo
r th
e 3
hr +
160
mg/
g gr
oup
CR
was
hi
gher
for
debr
ided
lesi
ons
(89%
) th
an n
on-
debr
ided
(78
%)
Lesi
on r
ecur
renc
e (e
valu
ated
in 9
7 pa
tient
s w
ith 2
99 le
sion
s th
at h
ad r
espo
nded
co
mpl
etel
y): T
he lo
wes
t re
curr
ence
rat
es
occu
rred
in t
he 3
hr +
160
mg/
g gr
oup
(11%
) co
mpa
red
with
bet
wee
n 26
% a
nd 4
5% fo
r th
e ot
her
grou
psPa
tient
s w
ho r
ecei
ved
two
PDT
ses
sion
s: Le
sion
rec
urre
nce
was
low
er fo
r th
e 1-
hr
and
3 hr
+ 1
60 m
g/g
grou
ps (
19%
and
17%
) th
an fo
r th
e 80
mg/
g gr
oups
(44
–45%
). Fo
r de
brid
ed le
sion
s in
the
3 h
r + 1
60 m
g/g
recu
rren
ce w
as 1
0% v
s 14
% fo
r no
n-de
brid
ed le
sion
sQ
oL a
nd r
etur
n to
nor
mal
act
ivit
y C
osm
etic
out
com
e (a
sses
sed
by V
AS
scor
e at
12
mth
) w
as r
ated
at
betw
een
8.4
cm a
nd
9.3
cm b
y bo
th in
vest
igat
or a
nd p
atie
nts
indi
catin
g an
exc
elle
nt c
osm
etic
out
com
eA
Es
Mos
t AEs
wer
e m
ild in
tens
ity a
nd t
he
maj
ority
wer
e lo
cal. T
he m
ost
com
mon
ly
repo
rted
AE
was
ery
them
a w
ith a
med
ian
dura
tion
of 1
7 d.
Oth
er A
Es in
clud
ed s
kin
pain
, pru
ritis
, bur
ning
sen
satio
n on
ski
n,
oede
ma
and
supp
urat
ion.
Fou
r pa
tient
s ex
peri
ence
d SA
Es b
ut t
hese
wer
e no
t co
nsid
ered
to
be t
reat
men
t re
late
dTr
eatm
ent-
rela
ted
AE
%:
1 hr
+ 1
60 m
g/g,
98%
3 hr
+ 1
60 m
g/g,
99%
1 hr
+ 8
0m/g
, 98%
3 hr
+ 8
0 m
g/g,
96%
Aut
hors
’ con
clus
ions
PD
T u
sing
a
1-hr
incu
batio
n w
ith 1
60 m
g/g
MA
L cr
eam
may
hav
e po
tent
ial f
or t
reat
ing
rela
tivel
y m
ild A
K le
sion
s an
d of
fers
pr
actic
al a
dvan
tage
s, bu
t re
gula
r su
bstit
utio
n is
not
rec
omm
ende
dB
rief
stu
dy a
ppra
isal
As
the
auth
ors
ackn
owle
dge,
the
re w
ere
som
e im
port
ant
flaw
s in
the
des
ign
of t
his
stud
y, in
clud
ing
the
lack
of b
lindi
ng o
f ou
tcom
e as
sess
ors,
and
havi
ng r
espo
nse
rate
judg
emen
ts m
ade
clin
ical
ly r
athe
r th
an h
isto
logi
cally
. Alth
ough
the
mea
n in
cuba
tion
and
illum
inat
ion
times
wer
e co
nsis
tent
acc
ordi
ng t
o th
e pr
otoc
ol,
it w
as c
lear
tha
t a
larg
e pr
opor
tion
of
patie
nts
rece
ived
onl
y 1
PDT
ses
sion
(w
hen
2 ar
e re
com
men
ded)
and
ar
ound
one
-thi
rd o
f les
ions
had
not
be
en d
ebri
ded.
Giv
en t
hat
the
prot
ocol
do
es n
ot a
ppea
r to
hav
e be
en fo
llow
ed
clos
ely,
or h
as n
ot u
tilis
ed P
DT
opt
imal
ly,
thes
e re
sults
sho
uld
be c
onsi
dere
d w
ith
caut
ion.
No
p-va
lues
or
form
al t
ests
of
stat
istic
al s
igni
fican
ce a
ppea
r to
hav
e be
en c
arri
ed o
ut, m
akin
g it
diffi
cult
to
asse
ss t
he r
eal d
iffer
ence
s be
twee
n tr
eatm
ent
grou
ps
d, d
ay(s
); hr
, hou
r(s)
; mth
, mon
th(s
); w
k, w
eek(
s); y
r, ye
ar(s
).
Appendix 13
188
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
189
Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Dra
giev
a et
al
. (20
04)42
Link
ed p
ublic
atio
ns16
1
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry S
witz
erla
ndLa
ngua
ge E
nglis
hSt
udy
desi
gn R
CT
No.
of p
arti
cipa
nts
Tota
l: 17
(34
lesi
onal
ar
eas
with
129
AK
; tw
o le
sion
al a
reas
pe
r pa
tient
wer
e ra
ndom
ised
for
trea
tmen
t)In
terv
entio
n: 1
7 le
sion
al a
reas
(62
AK
)C
ompa
rato
r: 17
le
sion
al a
reas
(67
AK
)N
o. o
f rec
ruit
ing
Cen
tres
One
Follo
w-u
p pe
riod
an
d fr
eque
ncy
FU
1, 4
, 8 a
nd 1
6 w
k af
ter
2nd
trea
tmen
t. A
Es
also
rec
orde
d at
the
se
times
and
bef
ore
and
afte
r ill
umin
atio
n
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
lesi
on
and
hist
olog
y M
ild t
o m
oder
ate
AK
Mai
n el
igib
ility
cri
teri
a M
ale
and
fem
ale
orga
n tr
ansp
lant
rec
ipie
nts
(18
or o
ver)
with
mild
to
mod
erat
e A
K (
confi
rmed
by
4-m
m p
unch
bio
psy
from
thi
ckes
t re
gion
). Pa
tient
s w
ith p
orph
yria
or
kno
wn
alle
rgy
to
com
poun
ds o
r ex
cipi
ents
of
the
cre
am w
ere
excl
uded
Pati
ent
char
acte
rist
ics
% M
ale:
76A
ge r
ange
: 44–
76 yr
Mea
n ag
e: 61
yrM
ost
lesi
ons
wer
e lo
cate
d on
the
face
or
scal
p. Le
sion
s w
ere
eith
er
untr
eate
d or
had
rec
eive
d pr
evio
us in
effe
ctiv
e tr
eatm
ent
over
1 m
th a
goC
onco
mit
ant
trea
tmen
t 1
g of
ora
l pa
race
tam
ol 1
hr
befo
re
illum
inat
ion
and
a fa
n w
as
used
on
the
affe
cted
are
a
Tria
l tre
atm
ents
MA
L–PD
T v
s PD
T
with
pla
cebo
cre
am (
with
in-p
artic
ipan
t co
mpa
riso
n)In
terv
enti
on M
AL–
PDT:
Tw
o co
nsec
utiv
e tr
eatm
ents
1 w
k ap
art,
perf
orm
ed o
n ar
eas
of m
axim
um s
ize
4 x
4 cm
. Sup
erfic
ial c
uret
tage
follo
wed
by
app
licat
ion
of 1
-mm
-thi
ck M
AL
crea
m
then
cov
ered
with
an
occl
usiv
e dr
essi
ng
for
3 hr
. Afte
r re
mov
al o
f dre
ssin
g an
d cl
eani
ng o
f are
a us
ing
salin
e so
lutio
n,
PDT
was
del
iver
ed a
t 80
mW
/cm
2 (7
5 J/c
m2 )
by
a no
n-co
here
nt li
ght
sour
ce
(em
issi
on s
pect
rum
600
–730
nm
)C
ompa
rato
r PD
T w
ith p
lace
bo c
ream
: A
s fo
r M
AL
but
with
pla
cebo
cre
am
Mor
bidi
ty W
eek
16: F
or t
he M
AL–
PDT
gr
oup
ther
e w
as C
R o
f 13/
17 le
sion
al a
reas
(9
5% C
I 9 t
o 16
) an
d PR
in 3
/17.
The
re
was
no
redu
ctio
n in
siz
e or
num
ber
of A
K
in 1
/17
MA
L–PD
T t
reat
ed a
rea
and
in a
ll pl
aceb
o-tr
eate
d ar
eas.
Ove
rall
lesi
on C
R r
ate
for
MA
L–PD
T w
as 5
6/62
and
for
plac
ebo
0/67
(p
= 0.
0003
)Q
oL a
nd r
etur
n to
nor
mal
act
ivit
y N
ot
asse
ssed
AE
s Fo
r th
e M
AL–
PDT
gro
up d
isco
mfo
rt
(usi
ng t
he V
AS
scal
e) w
as m
ild in
11/
17 a
nd
mod
erat
e in
6/1
7 (1
st il
lum
inat
ion)
– a
nd
mild
in 6
/17,
mod
erat
e in
9/1
7 an
d se
vere
in
2/1
7 (2
nd il
lum
inat
ion)
. Mild
to
mod
erat
e in
tens
ity A
Es fo
r th
e M
AL–
PDT
gro
up
incl
uded
ert
hyem
a, oe
dem
a an
d cr
ustin
g. Fo
r pl
aceb
o tr
eate
d ar
eas
disc
omfo
rt w
as m
ild
in a
ll ca
ses
Aut
hors
’ con
clus
ions
PD
T w
ith
met
hyl a
min
olev
ulin
ate
is s
afe
and
effe
ctiv
e fo
r AK
in t
rans
plan
t re
cipi
ents
. It
may
als
o re
duce
the
ris
k of
tr
ansf
orm
atio
n of
AK
s to
inva
sive
, and
po
tent
ially
fata
l, SC
CB
rief
stu
dy a
ppra
isal
Thi
s st
udy
was
ge
nera
lly o
f hig
h qu
ality
in m
etho
ds a
nd
repo
rtin
g. A
s th
e po
pula
tion
recr
uite
d w
ere
imm
unos
uppr
esse
d tr
ansp
lant
re
cipi
ents
the
res
ults
may
not
be
gene
ralis
able
to
othe
r po
pula
tions
Appendix 13
190
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
191Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Eri
cson
et a
l. (2
004)
43
Dat
a so
urce
Ful
l pub
lishe
d pa
per
Cou
ntry
Sw
eden
Lang
uage
Eng
lish
Stud
y de
sign
RC
TN
o. o
f par
tici
pant
sTo
tal:
40 (
37 a
naly
sed)
Inte
rven
tion:
Nin
e (b
road
fil
ter,
50 m
W/c
m2 )
Com
para
tor:
10 (
broa
d fil
ter,
75 m
W/c
m2 )
2nd
Com
para
tor:
Nin
e (n
arro
w fi
lter,
30 m
W/c
m2 )
3rd
Com
para
tor:
Nin
e (n
arro
w fi
lter,
45 m
W/c
m2 )
No.
of r
ecru
itin
g ce
ntre
s M
ultic
entr
eFo
llow
-up
peri
od a
nd
Freq
uenc
y 7
wk
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
lesi
on a
nd
hist
olog
y A
KM
ain
elig
ibili
ty c
rite
ria
Clin
ical
ly t
ypic
al A
K; e
ither
on
e A
K le
sion
, min
imum
di
amet
er o
f 20
mm
, or
thre
e le
sion
s w
ithin
are
a ex
ceed
ing
25 cm
2
Pati
ent
char
acte
rist
ics
% M
ale:
80M
ean
age:
71 yr
Lesi
ons
wer
e lo
cate
d on
th
e fa
ce, s
calp
, nec
k an
d up
per
ches
tC
onco
mit
ant
trea
tmen
t N
ot s
tate
d
Tria
l tre
atm
ents
ALA
–PD
T
50 m
W/c
m2 (
broa
d fil
ter)
vs A
LA–P
DT
75
mW
/cm
2 (br
oad
filte
r) v
s ALA
–PD
T
30 m
W/c
m2 (
narr
ow fi
lter)
vs A
LA–
PDT
45
mW
/cm
2 (na
rrow
filte
r). T
otal
do
se 1
00 J/
cm2 (
all t
reat
men
ts)
Inte
rven
tion
ALA
–PD
T: C
rust
s an
d sc
ales
wer
e re
mov
ed t
hen
20%
A
LA c
ream
was
app
lied
usin
g an
oc
clus
ive
band
age
and
rem
oved
afte
r 3
hr. T
he P
hoto
Dem
arca
tion
Syst
em
1, P
roto
type
5, w
as u
sed
to d
eliv
er
50 m
W/c
m2 ,
tota
l dos
e 10
0 J/c
m2 .
Fluo
resc
ence
imag
ing
reco
rdin
gs (
365
and
405
nm, 0
.5 m
W/c
m2 )
too
k pl
ace
befo
re t
reat
men
t, du
ring
tre
atm
ent
(afte
r 5,
10,
20
and
40 J/
cm2 )
and
afte
r fin
ishi
ng t
reat
men
t (1
00 J/
cm2 )
Com
para
tor A
LA–P
DT
with
75
mW
/cm
2 (br
oad
filte
r); o
ther
tr
eatm
ent
deta
ils a
s be
fore
2nd
com
para
tor A
LA–P
DT
with
30
mW
/cm
2 (na
rrow
filte
r); o
ther
tr
eatm
ent
deta
ils a
s be
fore
3rd
com
para
tor A
LA–P
DT
with
45
mW
/cm
2 (na
rrow
filte
r); o
ther
tr
eatm
ent
deta
ils a
s be
fore
Mor
bidi
ty T
here
was
a s
igni
fican
t co
rrel
atio
n be
twee
n flu
ence
rat
e an
d tr
eatm
ent
outc
ome
(p <
0.0
2);
the
high
est
num
ber
of p
atie
nts
with
com
plet
e re
mis
sion
was
in t
he
30 m
W/c
m2 (
narr
ow fi
lter)
gro
up (
8/9
patie
nts)
. The
re w
as a
non
-sig
nific
ant
tren
d to
war
ds a
sm
alle
r pr
opor
tion
of r
emai
ning
AK
for
the
narr
ow fi
lter
(p =
0.0
7). N
o si
gnifi
cant
diff
eren
ce w
as
foun
d be
twee
n 45
mW
/cm
2 (na
rrow
) an
d 50
mW
(br
oad)
gro
ups
impl
ying
pr
efer
able
tre
atm
ent
outc
ome
was
at
trib
utab
le t
o flu
ence
rat
e no
t sp
ectr
al e
mis
sion
QoL
and
ret
urn
to n
orm
al
acti
vity
Not
ass
esse
dA
Es T
here
was
no
sign
ifica
nt
corr
elat
ion
betw
een
fluen
ce r
ate
and
VAS
scor
e. T
he V
AS
valu
e in
crea
sed
up
to a
pea
k af
ter
a cu
mul
ativ
e lig
ht d
ose
of 2
0 J/c
m2
Aut
hors
’ con
clus
ions
Ph
otob
leac
hing
rat
e an
d pr
imar
y tr
eatm
ent
outc
omes
are
dep
ende
nt
on fl
uenc
e ra
te. A
low
flue
nce
rate
(3
0 m
W/c
m2 )
see
ms
pref
erab
le w
hen
perf
orm
ing
PDT
of A
K u
sing
non
-co
here
nt li
ght
sour
ces
Bri
ef s
tudy
app
rais
al T
he d
etai
ls o
f th
is s
mal
l tri
al w
ere
poor
ly r
epor
ted
ther
efor
e th
e re
liabi
lity
of t
he
conc
lusi
ons
is u
ncle
ar; h
owev
er, t
he
auth
ors
ackn
owle
dge
that
a la
rger
R
CT
is r
equi
red
Appendix 13
190
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
191
Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Fow
ler
and
Zax
(2
002)
44
Link
ed p
ublic
atio
ns16
2,16
3
Dat
a so
urce
Ful
l pub
lishe
d pa
per. A
sum
mar
y of
res
ults
of
2 t
rial
s w
ith id
entic
al
trea
tmen
t pr
otoc
ols.
Res
ults
fo
r m
ost
outc
omes
wer
e on
ly
avai
labl
e as
com
bine
d da
ta.
Furt
her
data
wer
e ob
tain
ed
from
dru
gs.c
om16
2
Cou
ntry
Not
sta
ted
Lang
uage
Eng
lish
Stud
y de
sign
RC
TN
o. o
f par
tici
pant
sTo
tal:
Rep
orte
d as
bei
ng 2
43,
acro
ss t
wo
tria
ls –
116
in
tria
l ALA
-018
, and
125
in t
rial
A
LA-0
19 (
whi
ch t
otal
s 24
1)In
terv
entio
n: A
LA-0
18: 8
7 A
LA-0
19: 9
3C
ompa
rato
r: A
LA-0
18: 2
9 A
LA-0
19: 3
2N
o. o
f rec
ruit
ing
cent
res
Mul
ticen
tre
Follo
w-u
p pe
riod
and
fr
eque
ncy
1, 4
, 8, a
nd 1
2 w
k, th
en F
U a
t in
terv
als
of
appr
oxim
atel
y 3
to 6
mth
, up
to 4
8 m
th
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
lesi
on a
nd
hist
olog
y A
KM
ain
elig
ibili
ty
crit
eria
Pat
ient
s w
ith
4–15
gra
de I
or II
AK
s on
the
face
or
scal
p. Ex
clud
ed p
atie
nts
had
a hi
stor
y of
cut
aneo
us
phot
osen
sitis
atio
n,
porp
hyri
a, hy
pers
ensi
tivity
to
por
phyr
ins,
phot
oder
mat
osis
or
inhe
rite
d or
acq
uire
d co
agul
atio
n de
fect
sPa
tien
t ch
arac
teri
stic
s%
Mal
e: 90
Age
ran
ge: 3
4–89
yrT
he n
umbe
r of
tre
ated
le
sion
s pe
r pa
tient
ran
ged
from
4 t
o 15
Trea
ted
area
s w
ere
the
face
or
scal
p, bu
t no
t bo
th
in t
he s
ame
patie
ntC
onco
mit
ant
trea
tmen
t N
ot s
tate
d
Tria
l tre
atm
ents
ALA
–PD
T
vs P
DT
with
pla
cebo
cre
amIn
terv
enti
on A
LA–P
DT:
To
pica
l 20%
ALA
and
10
J/cm
2 of
vis
ible
blu
e lig
ht (
from
th
e BL
U-U
illu
min
ator
, for
10
00 s)
wer
e ap
plie
d. L
esio
ns
that
had
not
cle
ared
wer
e re
-tre
ated
at
8 w
k an
d al
l pa
tient
s w
ere
re-e
valu
ated
at
12 w
k. A
fter
12-w
k lo
ng-t
erm
le
sion
rec
urre
nce
was
bas
ed
on c
ompl
ete
char
t re
view
(in
clud
ing
lesi
on p
hoto
grap
hs
and
trea
tmen
t du
ring
mos
t re
cent
pat
ient
vis
its a
t w
k 36
–48)
Com
para
tor
Not
des
crib
ed
Mor
bidi
tyAt
wk
8, C
R ra
te (1
00%
), by
no.
of p
atie
nts:
ALA
-018
: 60/
87 (
69%
) ALA
–PD
T v
s 4/
29 (
14%
) pl
aceb
oA
LA-0
19: 5
9/93
(63
%) A
LA–P
DT
vs
4/32
(13
%)
plac
ebo
At w
k 8,
> 7
5% c
lear
ance
rate
, by
no. o
f pat
ient
s:A
LA-0
18: 6
8/87
(78
%) A
LA–P
DT
vs
6/29
(21
%)
plac
ebo
ALA
-019
: 71/
93(7
6%) A
LA–P
DT
vs
8/32
(25
%)
plac
ebo
Whe
n re
sults
for
the
two
tria
ls w
ere
pool
ed, t
he C
R r
ate,
for
num
ber
of le
sion
s, w
as:
Lesi
on g
rade
I: 6
66/7
56 (
88%
) ALA
–PD
T v
s 12
2/30
2 (4
0%)
plac
ebo
Lesi
on g
rade
II: 4
95/6
32 (
78%
) ALA
–PD
T v
s 52
/199
(26
%)
plac
ebo
34%
of p
atie
nts
wer
e re
-tre
ated
at
8 w
kA
t w
k 12
CR
rat
e w
as 1
29/1
80 (
72%
) in
the
ALA
–PD
T g
roup
vs
7/6
1(11
%)
in p
lace
bo t
reat
ed p
atie
nts.
A r
espo
nse
rate
of
leas
t 75
% w
as r
epor
ted
in 1
58/1
80 (
88%
) of
ALA
–PD
T p
atie
nts
vs 1
2/61
(20%
) pl
aceb
o-tr
eate
d pa
tient
s. T
he c
lear
ance
rat
e w
as
high
er fo
r fa
cial
lesi
ons
than
sca
lp le
sion
sA
t 4
yr a
fter
PDT,
of 3
2 le
sion
s in
four
pat
ient
s (P
DT
gro
up),
69%
(22
) re
mai
ned
clea
red,
9%
(3)
wer
e ‘re
curr
ent’
and
22%
(7)
w
ere
‘unc
erta
in’.
Furt
her
resu
lts w
ere
repo
rted
QoL
and
ret
urn
to n
orm
al a
ctiv
ity
For A
LA–P
DT
cos
met
ic
resp
onse
was
rat
ed a
s ‘go
od’ t
o ‘e
xcel
lent
’ by
inve
stig
ator
s in
92
% o
f les
ions
; pat
ient
s ra
ted
cosm
etic
res
pons
e as
‘goo
d’ t
o ‘e
xcel
lent
’ in
94%
AK
lesi
ons;
85%
of p
atie
nts
prev
ious
ly t
reat
ed
with
5-F
U o
r cr
yoth
erap
y in
dica
ted
a pr
efer
ence
for A
LA–P
DT
fo
r fu
ture
man
agem
ent
AE
s Se
vere
stin
ging
and
/or
burn
ing
was
rep
orte
d by
at
leas
t 50
% o
f PD
T p
atie
nts;
less
tha
n 3%
sto
pped
tre
atm
ent.
In 9
9%
of P
DT
pat
ient
s, so
me
or a
ll le
sion
s w
ere
eryt
hem
atou
s sh
ortly
af
ter
trea
tmen
t vs
79%
in t
he p
lace
bo g
roup
. In
35%
of P
DT
pa
tient
s so
me
or a
ll le
sion
s w
ere
oede
mat
ous
vs 0
% in
the
pl
aceb
o gr
oup.
Both
typ
es o
f AE
reso
lved
or
impr
oved
by
4 w
k. M
ore
ALA
pat
ient
s al
so r
epor
ted
post
PDT
itch
ing
(26%
vs
7%)
Seve
n pa
tient
s ha
d an
SA
E –
all w
ere
deem
ed r
emot
ely,
or n
ot
rela
ted
to, t
reat
men
t
Aut
hors
’ co
nclu
sion
s The
ex
celle
nt s
hort
- an
d lo
ng-t
erm
co
smet
ic r
esul
ts,
low
rec
urre
nce
rate
and
hig
h ra
te
of p
atie
nt a
nd
phys
icia
n sa
tisfa
ctio
n as
soci
ated
with
A
LA–P
DT
indi
cate
de
finite
adv
anta
ges
over
oth
er e
xist
ing
trea
tmen
t m
odal
ities
fo
r AK
Bri
ef s
tudy
ap
prai
sal F
ew
met
hodo
logi
cal
deta
ils w
ere
repo
rted
, an
d de
tails
of t
he
stud
y po
pula
tion
wer
e un
clea
r. T
he s
ourc
es o
f in
form
atio
n ap
pear
ed
cont
radi
ctor
y in
re
port
ing
that
FU
bo
th c
ease
d at
12
mth
, and
als
o co
ntin
ued
for
4 yr
. T
he 4
-yr
resu
lts w
ere
pres
ente
d fo
r ju
st
four
pat
ient
s an
d th
is, c
oupl
ed w
ith
the
lack
of a
clin
ical
ly
rele
vant
com
pari
son
trea
tmen
t, fu
rthe
r qu
estio
ns t
he
relia
bilit
y of
the
au
thor
s’ c
oncl
usio
ns.
(Att
empt
s w
ere
mad
e to
con
tact
aut
hors
fo
r fu
rthe
r de
tails
.)
Appendix 13
192
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
193Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Fr
eem
an (
2003
)45
Link
ed
publ
icat
ions
164,
165
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry
Aus
tral
iaLa
ngua
ge E
nglis
hSt
udy
desi
gn
RC
TN
o. o
f pa
rtic
ipan
tsTo
tal:
204
Inte
rven
tion:
88
(360
AK
s) (
activ
e PD
T)
Com
para
tor:
23
(74
AK
s) (
plac
ebo
PDT
)2n
d C
ompa
rato
r: 89
(42
1 A
Ks)
(c
ryot
hera
py)
No.
of
recr
uiti
ng
cent
res
Nin
eFo
llow
-up
peri
od a
nd
freq
uenc
y FU
of
3 m
th (
afte
r a
run-
in p
erio
d of
up
to
2 w
k)
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
lesi
on a
nd
hist
olog
y M
ild t
o m
oder
ate
non-
pigm
ente
d A
KM
ain
elig
ibili
ty c
rite
ria
Patie
nts
with
mild
to
mod
erat
e no
n-pi
gmen
ted
AK
of
the
face
or
scal
p su
itabl
e fo
r cr
yoth
erap
y (w
ith t
he
larg
est
diam
eter
of e
ach
lesi
on
at le
ast
5 m
m)
Pati
ent
char
acte
rist
ics
% M
ale:
56 a
ctiv
e PD
T; 7
0 pl
aceb
o PD
T; 6
1 cr
yoth
erap
yM
ean
age:
64A
ge r
ange
: 33–
89 yr
Can
cer
stag
e:G
rade
I: 2
09 a
ctiv
e PD
T; 3
5 pl
aceb
o PD
T; 2
32 c
ryot
hera
pyG
rade
II: 1
51 a
ctiv
e PD
T; 3
9 pl
aceb
o PD
T; 4
5 cr
yoth
erap
y. A
ll pa
tient
s w
ere
Cau
casi
an,
mos
t ha
d Fi
tzpa
tric
k sk
in t
ype
I or
IIC
onco
mit
ant
trea
tmen
t N
ot s
tate
d
Tria
l tre
atm
ents
MA
L–PD
T v
s PD
T
with
pla
cebo
cre
am v
s co
nven
tiona
l cr
yoth
erap
yIn
terv
enti
on M
AL–
PDT:
Sca
les
and
crus
ts w
ere
rem
oved
and
lesi
on
surf
ace
roug
hene
d w
ith a
cur
ette
. MA
L cr
eam
(16
0 m
g/g)
was
app
lied
(1 m
m
thic
knes
s) u
nder
occ
lusi
on fo
r 3
hr
then
PD
T w
ith r
ed li
ght
(570
–670
nm
), in
tens
ities
of 5
0–25
0 m
W/c
m2 ,
tota
l do
se 7
5 J/c
m2 .
2 id
entic
al la
mps
(C
urel
ight
, Pho
tocu
re A
SA, O
slo)
ill
umin
ated
fiel
ds w
ith m
axim
um 5
.5cm
di
amet
er, m
ean
expo
sure
tim
e 10
min
w
ith a
max
imum
of s
ix t
reat
men
t si
tes
(map
ped
with
ace
tate
she
ets
and
AK
s m
arke
d) p
er p
atie
nt. A
nato
mic
al
land
mar
ks a
nd p
olar
oid
phot
ogra
phy
also
use
d. T
his
PDT
pro
cedu
re w
as
repe
ated
afte
r 7
dC
ompa
rato
r PD
T w
ith p
lace
bo:
As
for
MA
L–PD
T b
ut w
ith c
olou
r-m
atch
ed c
ream
bas
e in
stea
d of
MA
L2n
d co
mpa
rato
r C
ryot
hera
py: A
Ks
wer
e ou
tline
d an
d le
sion
s w
ere
froz
en
unifo
rmly
with
a 1
- to
2-m
m r
im. T
he
loca
lly a
ccep
ted
regi
men
was
use
d, i.
e.
the
prot
ocol
spe
cifie
d a
sing
le-t
imed
fr
eeze
–tha
w c
ycle
with
no
exac
t fr
eeze
tim
e (t
he t
ime
from
form
atio
n of
an
ice
ball
to c
omm
ence
men
t of
tha
win
g).
Lesi
ons
with
a m
ean
diam
eter
less
th
an 1
0 m
m h
ad a
mea
n (S
D)
free
ze
time
of 0
.12
s (0
.13)
; 10-
to
20-m
m
lesi
ons
0.16
s (0
.15)
and
mor
e th
an 2
0-m
m le
sion
s 0.
26 s
(0.1
1)
Mor
bidi
ty L
esio
n re
spon
se r
ate
was
sig
nific
antly
hi
gher
(91
%, 2
67/2
95)
in t
he M
AL–
PDT
gro
up,
than
the
pla
cebo
-PD
T g
roup
(30
%, 1
8/61
) an
d th
e cr
yoth
erap
y gr
oup
(68%
, 278
/407
), p
< 0.
001
for
both
. Res
pons
e ra
tes
wer
e hi
gher
in t
he t
hin
lesi
ons
than
the
mod
erat
ely
thic
k le
sion
s w
ith
MA
L–PD
T; in
the
cry
othe
rapy
gro
up, r
espo
nse
rate
s w
ere
high
er fo
r th
icke
r le
sion
sQ
oL a
nd r
etur
n to
nor
mal
act
ivit
y A
si
gnifi
cant
ly h
ighe
r pr
opor
tion
of M
AL–
PDT
pa
tient
s gr
aded
ove
rall
cosm
etic
out
com
e as
ex
celle
nt t
han
with
cry
othe
rapy
pat
ient
s (8
3%
vs 5
1% a
s as
sess
ed b
y in
vest
igat
or, p
< 0
.001
; 76%
vs
56%
as
asse
ssed
by
the
patie
nt, p
= 0
.013
). H
ypop
igm
enta
tion
was
pre
sent
in 5
% M
AL–
PDT
tre
ated
site
s vs
29%
cry
othe
rapy
site
s. H
yper
pigm
enta
tion,
sca
r fo
rmat
ion
or t
issu
e de
fect
s w
ere
pres
ent
in le
ss t
han
6% o
f tot
al
lesi
on s
ites.
MA
L–PD
T p
atie
nt s
atis
fact
ion
was
ra
ted
bett
er t
han
prev
ious
tre
atm
ent
in 6
1%,
equa
l in
24%
and
wor
se in
15%
. Pla
cebo
-PD
T
patie
nt s
atis
fact
ion
was
rat
ed b
ette
r th
an p
revi
ous
trea
tmen
t (c
ryot
hera
py, s
urge
ry o
r 5-
FU)
in 2
1%,
equa
l in
14%
and
wor
se in
64%
AE
s N
o sy
stem
ic A
Es w
ere
repo
rted
. The
mos
t co
mm
on A
Es w
ere
loca
l rea
ctio
ns (
74%
). 73
%
patie
nts
expe
rien
ced
at le
ast
1 lo
cal A
E af
ter
the
1st
PDT
ses
sion
and
66%
afte
r th
e 2n
d PD
T
sess
ion;
35%
afte
r cr
yoth
erap
y; 30
% a
fter
the
1st
and
27%
afte
r th
e 2n
d pl
aceb
o PD
T. M
ost
of t
he
AEs
in t
he M
AL–
PDT
gro
up w
ere
mild
(48
%)
or
mod
erat
e (4
0%)
inte
nsity
. Oth
er r
epor
ted
AEs
co
mm
on w
ith M
AL–
PDT
wer
e: bu
rnin
g se
nsat
ion,
st
ingi
ng, p
ainf
ul s
kin
(46%
), er
ythe
ma
(23.
9%),
oede
ma
(8.5
%),
skin
pee
ling
(5.1
%),
blis
ters
(3.
4%),
itchi
ng (
5.1%
) an
d cr
ustin
g (2
.3%
). M
edia
n du
ratio
n w
as 1
wk
or le
ss (
all e
vent
s). 1
MA
L–PD
T p
atie
nt
disc
ontin
ued
due
to t
he b
urni
ng s
ensa
tion
Aut
hors
’ con
clus
ions
PD
T
with
MA
L–PD
T is
an
exce
llent
tr
eatm
ent
optio
n, p
artic
ular
ly fo
r pa
tient
s w
ith w
ides
prea
d da
mag
e or
AK
lesi
ons
in c
osm
etic
ally
se
nsiti
ve a
reas
Bri
ef s
tudy
app
rais
al
Gen
eral
ly a
wel
l-con
duct
ed
and
repo
rted
stu
dy; a
lthou
gh
the
conc
lusi
ons
appe
ar li
kely
to
be r
elia
ble,
it s
houl
d be
not
ed
that
cry
othe
rapy
was
del
iver
ed
usin
g ‘lo
cally
acc
epte
d re
gim
ens’
al
low
ing
clin
ical
var
iatio
n be
twee
n th
e ni
ne c
entr
es
s, se
cond
(s).
Appendix 13
192
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
193Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Gup
ta (
2004
)35
Dat
a so
urce
Abs
trac
tC
ount
ry C
anad
aLa
ngua
ge E
nglis
hSt
udy
desi
gn R
CT
No.
of p
arti
cipa
nts
Tota
l: 50
Inte
rven
tion:
25
Com
para
tor:
25N
o. o
f rec
ruit
ing
cent
res
One
Follo
w-u
p pe
riod
and
fr
eque
ncy
FU a
t w
k 4,
8,
12
and
26
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
lesi
on a
nd
hist
olog
y A
KM
ain
elig
ibili
ty c
rite
ria
Part
icip
ants
with
5–2
0 le
sion
s of
mod
erat
e to
se
vere
AK
s w
ere
elig
ible
Pati
ent
char
acte
rist
ics
Not
sta
ted
Con
com
itan
t tr
eatm
ent
Not
sta
ted
Tria
l tre
atm
ents
ALA
–PD
T v
s 5-
FUIn
terv
enti
on A
LA–P
DT:
Incu
batio
n w
ith
ALA
for
45–6
0 m
in b
efor
e ill
umin
atio
n w
ith a
Blu
e Li
ght
PDT
Illu
min
ator
(40
0–45
0 nm
). Tre
atm
ent
repe
ated
at
wk
8 if
ther
e w
as le
ss t
han
a 75
% r
educ
tion
in
AK
s. N
o fu
rthe
r de
tails
rep
orte
dC
ompa
rato
r 5-
FU: A
pplic
atio
n of
5-F
U
to t
he fa
ce o
r sc
alp
twic
e da
ily fo
r 2–
4 w
k as
tol
erat
ed
Mor
bidi
ty N
ot a
sses
sed
QoL
and
ret
urn
to n
orm
al
acti
vity
Not
ass
esse
dA
Es A
t 1
wk
FU A
LA–P
DT
pa
tient
s sh
owed
few
sig
ns o
f ir
rita
tion
(ery
them
a, sc
alin
g an
d cr
ustin
g); 5
-FU
pat
ient
s ex
hibi
ted
mod
erat
e to
sev
ere
eryt
hem
a
Aut
hors
’ con
clus
ions
If s
hort
-dur
atio
n A
LA–P
DT
is s
how
n to
be
as e
ffect
ive
as
5% 5
-FU
at
wk
12 a
nd 2
6 th
en it
may
be
a su
itabl
e tr
eatm
ent
alte
rnat
ive
for
subj
ects
w
ith m
ultip
le m
oder
ate
to s
ever
e A
Ks
Bri
ef s
tudy
app
rais
al A
s th
ere
wer
e fe
w
deta
ils a
vaila
ble
in t
he a
bstr
act,
the
effic
acy
of t
he t
reat
men
ts w
as n
ot d
escr
ibed
an
d th
e st
udy
is n
ot y
et c
ompl
ete,
the
re
liabi
lity
of t
he a
utho
r’s c
oncl
usio
n is
un
clea
r. (A
ttem
pts
wer
e m
ade
to c
onta
ct
the
stud
y au
thor
.)
Appendix 13
194
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
195Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
H
ausc
hild
et a
l. (2
008)
,60 T
rial
A
K03
Link
ed
publ
icat
ions
166
Dat
a so
urce
Fu
ll pu
blis
hed
pape
rC
ount
ry
Ger
man
yLa
ngua
ge
Engl
ish
Stud
y de
sign
R
CT
No.
of
part
icip
ants
Tota
l: 10
3 (5
87
lesi
ons)
Inte
rven
tion:
69
Com
para
tor:
34N
o. o
f re
crui
ting
ce
ntre
s 29
(u
ncle
ar w
heth
er
this
was
for
each
tr
ial)
Follo
w-u
p pe
riod
and
fr
eque
ncy
FU
afte
r 12
wk
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
lesi
on a
nd h
isto
logy
A
KM
ain
elig
ibili
ty c
rite
ria
Cau
casi
an
mal
es a
nd fe
mal
es (
at le
ast
18 y
r ol
d) w
ith s
kin
type
s I–
IV w
ere
elig
ible
for
incl
usio
n. A
K le
sion
s ha
d to
be
mild
to
mod
erat
e (C
ockr
ell
defin
ition
) with
a m
axim
um d
iam
eter
of
1.8
cm a
nd in
terl
esio
nal d
ista
nce
of a
t le
ast
1 cm
. The
follo
win
g w
ere
excl
uded
: wom
en o
f chi
ld-
bear
ing
pote
ntia
l, no
n-re
spon
ders
to
pre
viou
s PD
T, pa
tient
s w
ith
part
icul
ar d
erm
atol
ogic
al c
ondi
tions
, po
rphy
ria,
dem
entia
or
clin
ical
ly
rele
vant
imm
unos
uppr
essi
on, t
opic
al
trea
tmen
t th
at m
ay a
ffect
res
pons
e 4
wk
befo
re a
nd d
urin
g th
e st
udy
(var
ious
cri
teri
a), t
reat
men
t w
ith
cyto
stat
ics
or r
adia
tion
3 m
th p
rior
to
/dur
ing
stud
y, an
d in
tole
ranc
e to
in
gred
ient
s of
ALA
Pati
ent
char
acte
rist
ics
% M
ale:
82M
ean
Age
: ALA
70.
4; P
lace
bo 7
1.4
Age
Ran
ge: 5
1–89
yrSk
in T
ype:
I 9%
; II 8
3%; I
II 1%
Con
com
itan
t tr
eatm
ent
Not
st
ated
Tria
l tre
atm
ents
ALA
–PD
T p
atch
vs
pla
cebo
PD
T p
atch
Inte
rven
tion
ALA
–PD
T: 3
–6
patc
hes
(4 cm
2 ) c
onta
inin
g 8
mg
of
5-A
LA w
as a
pplie
d to
lesi
ons
with
out
prep
arat
ion.
One
pat
ch p
er le
sion
. A
fter
4 h,
illu
min
atio
n w
ith r
ed li
ght
(37
J/cm
2 , 63
0 ±
3nm
) w
ith a
n LE
D
sour
ce. P
atie
nts
wer
e in
stru
cted
to
prot
ect
lesi
ons
from
ligh
t fo
r 48
h
afte
r th
erap
yC
ompa
rato
r Pl
aceb
o-PD
T: A
s fo
r A
LA–P
DT
but
with
pla
cebo
on
the
patc
hes
Mor
bidi
ty C
CC
R (
lesi
ons)
was
82%
(3
16/3
84)
for A
LA–P
DT
vs
19%
(34
/179
) fo
r pl
aceb
o, p
< 0
.000
1. C
orre
spon
ding
cl
eara
nce
rate
s on
a p
atie
nt b
asis
wer
e 62
% (
41/6
6) v
s 6%
(2/
33),
p <
0.00
01Q
oL a
nd r
etur
n to
nor
mal
act
ivit
y T
here
was
no
diffe
renc
e be
twee
n PD
T
or p
lace
bo in
the
cos
met
ic a
sses
smen
t of
‘cle
ared
lesi
ons’
(pa
tient
ass
essm
ent
p =
0.35
; inv
estig
ator
ass
essm
ent
0.54
). Pi
gmen
tatio
n st
atus
cla
ssed
as ‘
norm
al’
in t
he A
LA–P
DT
gro
ups
wer
e 91
% v
s 12
%. T
here
was
no
stat
istic
al d
iffer
ence
fr
om t
hose
tre
ated
with
pla
cebo
-PD
T
(p =
0.9
5). 9
5% o
f ALA
–PD
T p
atie
nts
wer
e ve
ry s
atis
fied
or s
atis
fied
with
the
ov
eral
l cos
met
ic o
utco
me
vs 4
4% w
ith
plac
ebo-
PDT.
Patie
nt s
atis
fact
ion
with
ov
eral
l out
com
e w
as g
reat
er w
ith P
DT
(p
< 0
.000
1)A
Es
One
AE
was
des
crib
ed a
s re
latin
g to
th
erap
y (t
rans
ient
dis
colo
ratio
n of
the
ski
n w
ith A
LA)
Tran
sien
t sk
in d
isco
lora
tion
in o
ne p
atie
nt
was
rel
ated
to
ALA
tre
atm
ent.
ALA
pa
tient
s ha
d m
ore
over
all l
ocal
rea
ctio
ns
whe
n tr
eatm
ent
was
app
lied
(mos
tly
itchi
ng, 4
2% v
s 13
%; t
he 1
3% p
lace
bo fi
gure
ap
pear
s to
be
pool
ed fr
om t
he 2
tri
als)
Aut
hors
’ con
clus
ions
ALA
–PD
T is
an
eas
y to
han
dle
one-
step
pro
cedu
re
for
ther
apy
of is
olat
ed m
ild t
o m
oder
ate
AK
lesi
ons.
Com
pare
d w
ith c
urre
nt P
DT
pro
cedu
res,
pre-
trea
tmen
t (e
.g. c
uret
tage
) is
not
ne
eded
and
han
dlin
g is
con
side
rabl
y fa
cilit
ated
. ALA
–PD
T le
ads
to e
ffica
cy
rate
s su
peri
or t
o pl
aceb
oB
rief
stu
dy a
ppra
isal
Thi
s st
udy
appe
ared
to
be g
ener
ally
wel
l co
nduc
ted;
how
ever
, it
was
unc
lear
ho
w m
any
cent
res
wer
e us
ed a
nd t
he
repo
rtin
g of
res
ults
was
som
etim
es
uncl
ear
CC
CR
, Com
plet
e cl
inic
al c
lear
ance
rat
e.
Appendix 13
194
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
195
Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Hau
schi
ld e
t al.
(200
8),60
Tri
al
AK
04Li
nked
pu
blic
atio
ns16
6
Dat
a so
urce
Fu
ll pu
blis
hed
pape
rC
ount
ry
Ger
man
yLa
ngua
ge
Engl
ish
Stud
y de
sign
R
CT
No.
of
part
icip
ants
Tota
l: 34
9 (1
950
lesi
ons)
Inte
rven
tion:
148
Com
para
tor:
149
(cry
osur
gery
)2n
d C
ompa
rato
r: 49
(pl
aceb
o)N
o. o
f re
crui
ting
ce
ntre
s 29
(u
ncle
ar w
heth
er
this
was
for
each
tr
ial)
Follo
w-u
p pe
riod
and
fr
eque
ncy
FU
afte
r 12
wk
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
lesi
on a
nd h
isto
logy
AK
Mai
n el
igib
ility
cri
teri
a C
auca
sian
m
ales
and
fem
ales
(at
leas
t 18
yr
old)
w
ith s
kin
type
s I–
IV w
ere
elig
ible
for
incl
usio
n. A
K le
sion
s ha
d to
be
mild
to
mod
erat
e (C
ockr
ell d
efini
tion)
with
a
max
imum
dia
met
er o
f 1.8
cm a
nd
inte
rles
iona
l dis
tanc
e of
at
leas
t 1
cm.
The
follo
win
g w
ere
excl
uded
: wom
en o
f ch
ild-b
eari
ng p
oten
tial,
non-
resp
onde
rs
to p
revi
ous
PDT,
patie
nts
with
pa
rtic
ular
der
mat
olog
ical
con
ditio
ns,
porp
hyri
a, de
men
tia o
r cl
inic
ally
rel
evan
t im
mun
osup
pres
sion
, top
ical
tre
atm
ent
that
may
affe
ct r
espo
nse
4 w
k be
fore
an
d du
ring
the
stu
dy (
vari
ous
crite
ria)
, tr
eatm
ent
with
cyt
osta
tics
or r
adia
tion
3 m
th p
rior
to/
duri
ng s
tudy
and
in
tole
ranc
e to
ingr
edie
nts
of p
lace
bo o
r kn
own
reac
tions
to
cryo
ther
apy
Pati
ent
char
acte
rist
ics
% M
ale:
72M
ean
age:
PDT
70,
cry
osur
gery
71,
pl
aceb
o 72
Age
ran
ge: 4
1–94
yrSk
in t
ype:
I 18%
, II 6
6%, I
II 15
%, I
V 1
%C
onco
mit
ant
trea
tmen
t N
ot s
tate
d
Tria
l tre
atm
ents
ALA
–PD
T p
atch
vs
cryo
surg
ery
vs
Plac
ebo
PDT
pat
chIn
terv
enti
on A
LA–P
DT
pat
ch:
4–8
patc
hes
(4 cm
2 ) c
onta
inin
g 8
mg
of 5
-ALA
wer
e ap
plie
d to
le
sion
s w
ithou
t pr
epar
atio
n,
one
patc
h pe
r le
sion
. Afte
r 4
hr, i
llum
inat
ion
with
red
ligh
t (3
7 J/c
m2 ,
630
± 3
nm)
with
O
mni
lux
(11
cent
res)
. Pat
ient
s w
ere
inst
ruct
ed t
o pr
otec
t le
sion
s fr
om li
ght
for
48 h
r af
ter
ther
apy
Com
para
tor
cryo
surg
ery:
A s
tand
ardi
sed
prot
ocol
was
us
ed. O
pen
spra
ying
pro
cedu
re
with
liqu
id n
itrog
en in
1 c
ycle
w
as u
sed
(with
siz
e C
noz
zles
) an
d fr
eeze
tim
e (o
f 5–1
0 s)
st
arte
d af
ter
ice
ball
form
atio
n2n
d co
mpa
rato
r Pl
aceb
o PD
T p
atch
: As
for A
LA–P
DT
bu
t w
ith p
lace
bo o
n th
e pa
tche
s
Mor
bidi
ty T
he c
ompl
ete
clin
ical
cle
aran
ce r
ates
(le
sion
s) w
ere
89%
(66
4/75
0) fo
r ALA
–PD
T, 77
%
(530
/692
) fo
r cr
yosu
rger
y an
d 29
% (
75/2
59)
for
plac
ebo.
PD
T w
as s
igni
fican
tly b
ette
r th
an p
lace
bo
PDT
(p
< 0.
001)
and
cry
osur
gery
(p
= 0.
007)
. C
lear
ance
rat
es (
patie
nts)
wer
e A
LA–P
DT
67%
(8
6/12
9), c
ryos
urge
ry 5
2% (
66/1
26)
and
plac
ebo
12%
(5
/43)
. PD
T w
as s
igni
fican
tly b
ette
r th
an p
lace
bo a
nd
cryo
surg
ery
(p <
0.0
01 fo
r bo
th)
QoL
and
ret
urn
to n
orm
al a
ctiv
ity
Patie
nts’
an
d in
vest
igat
ors’
ass
essm
ent
of c
osm
etic
out
com
e of
cle
ared
lesi
ons
was
sig
nific
antly
bet
ter
for A
LA–
PDT
tha
n cr
yosu
rger
y (p
< 0
.001
). 95
% o
f ALA
–PD
T
patie
nts
wer
e ve
ry s
atis
fied
or s
atis
fied
with
the
ov
eral
l cos
met
ic o
utco
me
vs 8
2% w
ith c
ryos
urge
ry.
It ap
pear
s to
be
repo
rted
tha
t ALA
pat
ient
s w
ere
sign
ifica
ntly
mor
e sa
tisfie
d th
an p
lace
bo
and
cryo
surg
ery
(p <
0.0
001)
. Pig
men
tatio
n st
atus
cl
asse
d as
‘nor
mal
’ in
the
ALA
–PD
T g
roup
s w
as
88%
. Hyp
opig
men
tatio
n w
as s
een
in 3
3% o
f les
ions
w
ith c
ryos
urge
ry. H
yper
pigm
enta
tion
was
see
n in
9%
PD
T p
atie
nts
vs 4
% p
lace
bo. P
igm
enta
tion
stat
us
was
sig
nific
antly
diff
eren
t be
twee
n A
LA–P
DT
and
cr
yosu
rger
y (p
< 0
.001
) bu
t th
e di
ffere
nce
betw
een
ALA
–PD
T a
nd p
lace
bo w
as n
ot s
igni
fican
t (p
= 0
.87)
AE
s Thr
ee p
er c
ent
in t
he A
LA a
nd c
ryos
urge
ry
arm
s an
d 2%
pla
cebo
rep
orte
d an
AE
rela
ted
to
ther
apy.
99%
of A
LA p
atie
nts
expe
rien
ced
an a
dver
se
reac
tion
at s
ome
stag
e of
tre
atm
ent
(pla
cebo
dat
a w
as p
oole
d w
ith t
rial
AK
03)
Aut
hors
’ con
clus
ions
A
LA–P
DT
is a
n ea
sy t
o ha
ndle
one
-ste
p pr
oced
ure
for
ther
apy
of is
olat
ed m
ild
to m
oder
ate
AK
lesi
ons.
Com
pare
d w
ith c
urre
nt P
DT
pr
oced
ures
, pre
-tre
atm
ent
is n
ot n
eede
d an
d ha
ndlin
g is
con
side
rabl
y fa
cilit
ated
. A
sin
gle
PDT
tre
atm
ent
resu
lts in
effi
cacy
rat
es b
eing
st
atis
tical
ly s
igni
fican
tly
supe
rior
to
plac
ebo
and
cryo
surg
ery
Bri
ef s
tudy
app
rais
al T
he
stud
y ap
pear
s to
be
gene
rally
w
ell c
ondu
cted
but
rep
ortin
g of
som
e of
the
met
hodo
logy
an
d re
sults
was
unc
lear
Appendix 13
196
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
197Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Hau
schi
ld
et a
l. (20
08)55
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry G
erm
any
Lang
uage
Eng
lish
Stud
y de
sign
R
CT
No.
of
part
icip
ants
Tota
l: 14
9: 1
46
patie
nts
com
plet
ed
stud
y, of
whi
ch 1
40
(520
lesi
ons)
wer
e in
the
per
pro
toco
l po
pula
tion
Inte
rven
tion:
34
(128
lesi
ons)
0.5
-hr
incu
batio
nC
ompa
rato
r: 38
(1
38 le
sion
s) 1
-hr
incu
batio
n2n
d C
ompa
rato
r: 34
(12
4 le
sion
s)
2-hr
incu
batio
n3r
d C
ompa
rato
r: 34
(13
0 le
sion
s)
4-hr
incu
batio
nN
o. o
f rec
ruit
ing
cent
res
12Fo
llow
-up
peri
od
and
freq
uenc
y 4
and
8 w
k af
ter
trea
tmen
t
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
lesi
on a
nd h
isto
logy
AK
(m
ild t
o m
oder
ate)
Mai
n el
igib
ility
cri
teri
a C
auca
sian
m
ales
or
fem
ales
age
d at
leas
t 18
yr
with
his
tolo
gica
lly c
onfir
med
mild
to
mod
erat
e A
K. L
esio
ns w
ere
requ
ired
to
have
max
imum
dia
met
er o
f 1.8
cm a
nd
inte
rles
iona
l dis
tanc
e of
at
leas
t 1
cm.
Patie
nts
with
der
mat
olog
ical
con
ditio
ns
likel
y to
impa
ct o
n re
sults
wer
e ex
clud
ed. F
urth
er e
ligib
ility
cri
teri
a w
ere
repo
rted
Pati
ent
char
acte
rist
ics
% M
ale:
74A
ge r
ange
: 39–
91 yr
acr
oss
grou
psM
ean
age:
72 yr
, 72
yr, 7
0 yr
, 70
yr,
resp
ectiv
ely,
for
the
four
tre
atm
ent
grou
psM
ost
lesi
ons
wer
e lo
cate
d on
the
sca
lp
or fo
rehe
ad in
all
grou
ps, s
ever
ity w
as
fair
ly e
venl
y sp
lit b
etw
een
mild
and
m
oder
ate.
Mea
n le
sion
dia
met
er w
as
sim
ilar
acro
ss g
roup
s at
aro
und
8–9
cmC
onco
mit
ant
trea
tmen
t A
ny
othe
r to
pica
l tre
atm
ent
able
to
affe
ct
AK
not
per
mitt
ed 4
wk
prio
r to
and
du
ring
stu
dy. N
o ur
ea a
nd s
alic
ylic
aci
d-co
ntai
ning
pre
para
tions
per
mitt
ed 2
wk
prio
r an
d du
ring
stu
dy
Tria
l tre
atm
ents
Pat
ch c
onta
inin
g A
LA (
PD
P 50
6 A
) ap
plie
d to
lesi
ons
for
0.5,
1, 2
or
4 hr
fo
llow
ed b
y ill
umin
atio
n w
ith r
ed li
ght
Inte
rven
tion
PD
T p
atch
+ 0
.5-h
r in
cuba
tion:
Be
twee
n th
ree
and
four
lesi
ons
per
patie
nt
wer
e tr
eate
d us
ing
a PD
T p
atch
(on
e pa
tch
per
lesi
on)
cont
aini
ng 8
mg
of A
LA. P
atch
is
ligh
tpro
of t
here
fore
pro
vide
s oc
clus
ive
prot
ectio
n. A
fter
patc
h w
as r
emov
ed, l
esio
n ill
umin
ated
with
red
ligh
t (d
ose
37 J/
cm2 ,
wav
elen
gth
arou
nd 6
30 n
m).
Furt
her
PDT
pa
ram
eter
s w
ere
not
repo
rted
Com
para
tor
PDT
pat
ch +
1-h
r in
cuba
tion:
se
e ab
ove
2nd
com
para
tor
PDT
pat
ch +
2-h
r in
cuba
tion:
see
abo
ve3r
d co
mpa
rato
r PD
T p
atch
+ 4
-hr
incu
batio
n: s
ee a
bove
Mor
bidi
ty T
he m
ajor
ity o
f les
ions
sh
owed
cle
aran
ce 8
wk
afte
r PD
T a
nd
the
4-hr
incu
batio
n gr
oup
show
ed t
he
best
res
pons
e –
estim
ated
86%
cle
aran
ce
rate
and
thi
s w
as ‘s
tatis
tical
ly s
elec
ted
as
the
best
tre
atm
ent’.
All
but
1 of
the
12
cent
res
foun
d si
mila
r re
sults
(de
tails
not
re
port
ed).
In s
ome
patie
nts,
lesi
ons
that
ap
pear
ed ‘c
lear
ed’ a
t w
k 4
then
wor
sene
d by
wk
8 –
this
effe
ct w
as m
ost
appa
rent
in
the
0.5
-hr
grou
p, an
d w
as n
ot p
rese
nt
in t
he 4
-hr
grou
pQ
oL a
nd r
etur
n to
nor
mal
act
ivit
y N
ot a
sses
sed
AE
s Fi
ve p
atie
nts
repo
rted
AE
cons
ider
ed t
o be
rel
ated
to
the
stud
y tr
eatm
ent:
head
ache
, mod
erat
e ep
ista
xis
and
mild
incr
ease
of a
lani
ne t
rans
amin
ase.
Lo
cal r
eact
ions
dur
ing
appl
icat
ion
and
incu
batio
n in
clud
ed b
urni
ng, p
ruri
tis a
nd
eryt
hem
a –
all b
ut o
ne c
ase
was
rat
ed
as m
ild o
r m
oder
ate.
Loc
al r
eact
ions
du
ring
illu
min
atio
n ap
pear
ed t
o be
do
se d
epen
dent
and
ran
ged
from
26%
in
the
0.5
-hr
grou
p to
66%
in t
he 4
-hr
grou
p. M
ost
freq
uent
rea
ctio
ns w
ere
pain
, bur
ning
and
pru
ritis
. One
pat
ient
’s tr
eatm
ent
was
inte
rrup
ted
due
to
seve
re p
ain.
Alm
ost
all p
atie
nts
had
loca
l re
actio
ns a
fter
trea
tmen
t, w
ith e
ryth
ema,
scab
bing
, des
quam
atio
n, b
urni
ng a
nd
prur
itis
bein
g co
mm
on. P
atie
nts
with
cl
eara
nce
expe
rien
ced
loca
l rea
ctio
ns t
o a
grea
ter
exte
nt t
han
patie
nts
with
out
clea
ranc
e
Aut
hors
’ con
clus
ions
PD
P 5
06 A
-PD
T p
atch
es
are
suita
ble
for
the
trea
tmen
t of
up
to e
ight
A
K le
sion
s of
mild
to
mod
erat
e in
tens
ity o
n th
e he
ad a
nd fa
ce, a
nd
4-hr
app
licat
ion
resu
lts
in e
xcel
lent
out
com
es.
Furt
her
Phas
e III
tri
als
are
requ
ired
to c
onfir
m
thes
e ou
tcom
esB
rief
stu
dy a
ppra
isal
T
his
stud
y w
as r
elat
ivel
y po
orly
rep
orte
d m
akin
g it
diffi
cult
to
asse
ss t
he r
elia
bilit
y of
the
met
hodo
logy
or
res
ults
. The
use
of
mul
tiple
cen
tres
in a
sm
all t
rial
rai
ses
the
poss
ibili
ty o
f cen
tre-
effe
cts
on t
reat
men
t an
d ou
tcom
es. P
atie
nts
wer
e on
ly fo
llow
ed u
p fo
r 8
wk.
No
stat
istic
al t
est
resu
lts w
ere
repo
rted
; th
eref
ore
it is
diffi
cult
to b
e co
nfide
nt in
the
co
nclu
sion
s of
effi
cacy
Appendix 13
196
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
197Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Jeffe
s et
al
. (19
98)41
Dat
a so
urce
A
bstr
act
Cou
ntry
USA
Lang
uage
Eng
lish
Stud
y de
sign
R
CT
No.
of
part
icip
ants
Tota
l: 36
Inte
rven
tion:
36
Com
para
tor:
36N
o. o
f rec
ruit
ing
cent
res
Not
st
ated
mul
ticen
tre
Follo
w-u
p pe
riod
and
fr
eque
ncy
8 an
d 16
wk
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
lesi
on
and
hist
olog
y A
KM
ain
elig
ibili
ty
crit
eria
Pat
ient
s w
ith fo
ur A
Ks
on
the
face
and
sca
lpPa
tien
t ch
arac
teri
stic
s N
ot s
tate
dC
onco
mit
ant
trea
tmen
t N
ot
stat
ed
Tria
l tre
atm
ents
ALA
–PD
T v
s PD
T w
ith
plac
ebo
(with
in-p
artic
ipan
t co
mpa
riso
n)In
terv
enti
on A
LA–P
DT:
Tw
o A
Ks
wer
e tr
eate
d w
ith 2
0% A
LA s
olut
ion
(Lev
ulan
) an
d af
ter
14-
to 1
8-hr
exp
osed
to
blue
(n
on-la
ser)
ligh
t at
dos
es o
f 2, 5
and
10
J/cm
2 . Pa
tient
s w
ere
re-t
reat
ed a
t 8
wk
if ne
cess
ary.
Furt
her
PDT
par
amet
ers
wer
e no
t re
port
edC
ompa
rato
r Pl
aceb
o PD
T: A
s ab
ove
exce
pt p
lace
bo c
ontr
ol w
as u
sed
in p
lace
of
ALA
sol
utio
n
Mor
bidi
ty A
t 8
wk,
66%
of A
Ks
trea
ted
with
ALA
had
a C
R v
s 17
% w
ith p
lace
bo
(p <
0.0
01).
At
16 w
k. C
R w
as s
een
in 5
6/66
(8
5%)
of A
LA–P
DT
pat
ient
s (n
o re
sults
re
port
ed fo
r pl
aceb
o). A
Ks
trea
ted
with
A
LA–P
DT
at
5 or
10
J/cm
2 of l
ight
res
ulte
d in
a s
igni
fican
tly b
ette
r re
spon
se t
han
the
corr
espo
ndin
g pl
aceb
o gr
oup,
alth
ough
th
ere
was
no
sign
ifica
nt d
iffer
ence
bet
wee
n th
e gr
oups
at
2 J/c
m2
QoL
and
ret
urn
to n
orm
al a
ctiv
ity
Not
as
sess
edA
Es T
he a
utho
rs r
epor
ted
that
hy
perp
igm
enta
tion
was
see
n in
11%
of
AK
s tr
eate
d w
ith A
LA–P
DT,
whi
ch w
as
not
diffe
rent
from
the
pla
cebo
gro
up.
The
tre
atm
ent
was
wel
l tol
erat
ed a
nd n
o pa
tient
s w
ithdr
ew d
ue t
o an
AE
Aut
hors
’ con
clus
ions
The
aut
hors
did
no
t re
port
any
con
clus
ions
Bri
ef s
tudy
app
rais
al L
ittle
use
ful
evid
ence
cou
ld b
e re
trie
ved
from
thi
s ab
stra
ct w
hich
pro
vide
d ve
ry fe
w
met
hodo
logi
cal o
r re
sult
deta
ils, a
nd
invo
lved
a fa
irly
sm
all s
ampl
e fo
llow
ed u
p fo
r 16
wk
Appendix 13
198
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
199Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Kau
fman
n et
al
. (20
08)46
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ries
Aus
tral
ia,
Belg
ium
, Ger
man
y, U
KLa
ngua
ge E
nglis
hSt
udy
desi
gn R
CT
No.
of p
arti
cipa
nts
Tota
l: 12
1 (1
343
lesi
ons)
Inte
rven
tion:
121
(69
1 le
sion
s)C
ompa
rato
r: 12
1 (6
52
lesi
ons)
No.
of r
ecru
itin
g ce
ntre
s 24
Follo
w-u
p pe
riod
an
d fr
eque
ncy
FU
at w
k 12
and
24.
A
dditi
onal
tel
epho
ne
calls
wer
e m
ade
at w
k 1
and
13 w
hen
patie
nts
wer
e re
-tre
ated
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
lesi
on
and
hist
olog
y N
on-
hype
rker
atot
ic A
KM
ain
elig
ibili
ty c
rite
ria
Mal
es a
nd n
on-p
regn
ant
wom
en a
ged
18 o
r ov
er,
with
a c
linic
al d
iagn
osis
of
non-
hype
rker
atot
ic A
K, o
f m
ild o
r m
oder
ate
thic
knes
s, on
loca
tions
oth
er t
han
the
face
or
scal
p, w
ere
elig
ible
fo
r in
clus
ion.
Pat
ient
s ha
d to
ha
ve a
t le
ast
four
com
para
ble
sym
met
rica
l AK
s, of
sim
ilar
seve
rity
and
tot
al n
umbe
r on
bot
h si
des
of t
he b
ody.
Furt
her
elig
ibili
ty c
rite
ria
wer
e re
port
edPa
tien
t ch
arac
teri
stic
s%
Mal
e: 65
Age
ran
ge: 3
8–89
yrM
ean
age:
68.9
yrC
ance
r st
age:
Gra
de I,
687
; gr
ade
II, 6
56Pa
tient
s ha
d (a
mea
n of
) si
x le
sion
s pe
r si
de. F
urth
er
patie
nt c
hara
cter
istic
s w
ere
repo
rted
Con
com
itan
t tr
eatm
ent
Not
sta
ted
Tria
l tre
atm
ents
MA
L–PD
T
vs c
ryot
hera
py (
with
in-
part
icip
ant
com
pari
son)
Inte
rven
tion
MA
L–PD
T:
Afte
r sc
rapi
ng o
f les
ions
, a
1-m
m la
yer
of 1
60-m
g/g
MA
L cr
eam
was
app
lied
to
each
lesi
on (
incl
udin
g 5
mm
of
sur
roun
ding
tis
sue)
for
3 hr
(un
der
occl
usio
n). A
fter
salin
e cl
eans
ing,
a st
anda
rd
LED
lam
p ill
umin
ated
lesi
ons
with
nar
row
ban
d re
d lig
ht (
aver
age
630
nm, d
ose
37 J/
cm2 ,
mea
n tim
e 8
min
36
s). L
esio
ns w
ith a
non
-CR
w
ere
re-t
reat
ed a
fter
12 w
kC
ompa
rato
r C
ryot
hera
py:
Dou
ble
free
ze–t
haw
cr
yoth
erap
y us
ing
liqui
d ni
trog
en s
pray
app
lied
with
a
1- t
o 2-
mm
froz
en r
im
outs
ide
the
lesi
on o
utlin
e.
Tim
ing
of fr
eeze
–tha
w
appl
icat
ion
was
as
per
usua
l pr
actic
e of
eac
h ce
ntre
(m
ean
time
20 s
± 14
s)
Mor
bidi
ty A
t w
k 24
the
mea
n re
duct
ion
in le
sion
cou
nt fr
om
base
line
was
78%
for
MA
L–PD
T a
nd 8
8% fo
r cr
yoth
erap
y (p
er-p
roto
col p
opul
atio
n) (
p =
0.00
2), 9
5% C
I of t
he b
ilate
ral
diffe
renc
e (M
AL–
PDT
/cry
othe
rapy
) w
as b
etw
een
–16.
6% a
nd
3.9%
. IT
T (
last
obs
erva
tion
carr
ied
forw
ard)
ana
lysi
s co
nfirm
ed
this
(75
% r
educ
tion
with
MA
L–PD
T v
s 87
% w
ith c
ryot
hera
py,
p <
0.00
1). 7
6% (
455)
of l
esio
ns w
ere
cure
d w
ith M
AL–
PDT
vs
88%
(49
0) w
ith c
ryot
hera
py. T
he d
iffer
ence
was
sim
ilar
for
mild
- an
d m
oder
ate-
thic
knes
s le
sion
sQ
oL a
nd r
etur
n to
nor
mal
act
ivit
y In
vest
igat
or-a
sses
sed
cosm
etic
out
com
e w
as s
igni
fican
tly b
ette
r fo
r M
AL–
PDT
tha
n cr
yoth
erap
y (p
< 0
.001
). In
the
MA
L–PD
T g
roup
, 79%
of l
esio
ns
had
an e
xcel
lent
cos
met
ic o
utco
me,
19%
goo
d, 3
% fa
ir a
nd 0
%
poor
(co
mpa
red
with
56%
exc
elle
nt, 3
6% g
ood,
8%
fair
and
0.
9% p
oor
with
cry
othe
rapy
). A
fter
24 w
k, 50
% o
f pat
ient
s pr
efer
red
MA
L–PD
T in
ter
ms
of c
osm
etic
out
com
e co
mpa
red
with
22%
for
cryo
ther
apy
(p <
0.0
01).
28%
had
no
pref
eren
ce
(ITT
ana
lysi
s). P
atie
nts
pref
erre
d M
AL–
PDT
to
cryo
ther
apy
for
all q
uest
ions
in t
he p
atie
nt q
uest
ionn
aire
(be
twee
n 12
% a
nd
58%
of d
iffer
ence
). The
diff
eren
ces
wer
e m
arke
d ap
art
from
ef
fect
iven
ess
of t
reat
men
t (3
9% fa
vour
ed M
AL–
PDT
vs
26%
cr
yoth
erap
y, no
t si
gnifi
cant
). Pa
tient
s pr
efer
red
MA
L–PD
T in
te
rms
of c
omfo
rt (
60%
vs
10%
, p <
0.0
01),
proc
edur
e (4
9%
vs 2
8%, p
= 0
.05)
and
hea
ling
(64%
vs
6%, p
< 0
.001
). O
vera
ll pa
tient
sat
isfa
ctio
n fa
vour
ed M
AL–
PDT
(49
% v
s 20
%, p
< 0
.001
). If
re-t
reat
men
t w
as r
equi
red
59%
wou
ld p
refe
r M
AL–
PDT
ove
r cr
yoth
erap
y (2
5%, p
< 0
.001
)A
Es T
here
wer
e 63
% p
atie
nts
with
99
AEs
with
cry
othe
rapy
vs
45%
pat
ient
s w
ith 6
7 A
Es w
ith M
AL–
PDT.
Mos
t w
ere
derm
atol
ogic
al a
nd r
elat
ed t
o tr
eatm
ent.
The
mos
t co
mm
only
re
port
ed A
E fo
r M
AL–
PDT
was
pho
tose
nsiti
vity
rea
ctio
n (4
3% o
f pat
ient
s w
ith 6
3 A
Es)
and
cold
exp
osur
e in
jury
for
cryo
ther
apy
(62%
pat
ient
s w
ith 9
5 A
Es).
Mos
t w
ere
of m
ild
inte
nsity
. Tw
o pa
tient
s in
the
cry
othe
rapy
gro
up r
epor
ted
seve
re c
old
expo
sure
inju
ry
Aut
hors
’ con
clus
ions
M
AL–
PDT
sho
wed
in
feri
or e
ffica
cy fo
r tr
eatm
ent
of n
on-fa
ce/
scal
p A
K c
ompa
red
with
cr
yoth
erap
y. H
owev
er,
both
tre
atm
ents
sho
wed
hi
gh e
ffica
cy, a
nd M
AL–
PDT
con
veye
d th
e ad
vant
ages
of b
ette
r co
smes
is a
nd h
ighe
r pa
tient
pre
fere
nce
Bri
ef s
tudy
app
rais
al
The
stu
dy w
as q
uite
w
ell c
ondu
cted
, but
it
was
ope
n in
des
ign
and
ther
efor
e th
ere
was
po
tent
ial f
or in
vest
igat
or/
patie
nt b
ias.
The
po
ssib
ility
of i
nstit
utio
nal
diffe
renc
es a
nd/o
r pr
otoc
ol d
evia
tion
(24
cent
res
in fo
ur c
ount
ries
) af
fect
ing
the
relia
bilit
y of
res
ults
was
illu
stra
ted
by t
he w
ide
vari
atio
n of
fr
eeze
–tha
w t
imin
gs u
sed
for
cryo
ther
apy
Appendix 13
198
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
199Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Kur
wa
et a
l. (1
999)
47
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry U
KLa
ngua
ge E
nglis
hSt
udy
desi
gn R
CT
No.
of p
arti
cipa
nts
Tota
l: 17
Inte
rven
tion:
17
Com
para
tor:
17N
o. o
f rec
ruit
ing
cent
res
Not
sta
ted
Follo
w-u
p pe
riod
an
d fr
eque
ncy
1 w
k, 4
wk
and
6 m
th
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
lesi
on a
nd
hist
olog
y A
KM
ain
elig
ibili
ty c
rite
ria
It ap
pear
ed t
hat
patie
nts
with
a
long
his
tory
of A
Ks
affe
ctin
g th
e fo
rear
ms
and
hand
s w
ere
elig
ible
for
incl
usio
nPa
tien
t ch
arac
teri
stic
s%
Mal
e: 47
Age
ran
ge: 5
3–79
yrC
onco
mit
ant
trea
tmen
t N
ot s
tate
d
Tria
l tre
atm
ents
ALA
–PD
T
vs 5
-FU
(w
ithin
-par
ticip
ant
com
pari
son)
Inte
rven
tion
ALA
–PD
T:
Thi
ck s
urfa
ce s
cale
was
re
mov
ed if
pre
sent
the
n 20
%
5-A
LA w
as a
pplie
d to
pica
lly
and
cove
red
in a
ligh
t-im
perm
eabl
e dr
essi
ng fo
r 4
hr.
PDT
was
adm
inis
tere
d w
ith
a ha
loge
n la
mp
(580
–740
nm
, 15
0 J/c
m2 ,
mea
n flu
ence
rat
e 80
mW
/cm
2 )C
ompa
rato
r 5-
FU c
ream
(5
%)
was
app
lied
topi
cally
tw
ice
a da
y to
one
han
d fo
r 3
wk
by t
horo
ugh
mas
sage
Mor
bidi
ty T
he m
ean
lesi
onal
are
a be
fore
tre
atm
ent
for
PDT
was
132
2 m
m2 a
nd 6
mth
afte
r tr
eatm
ent
was
291
mm
2 (a
red
uctio
n of
73%
, 95%
CI 6
1% t
o 84
%).
For
5-FU
, mea
n le
sion
al a
rea
was
139
0 m
m2 b
efor
e tr
eatm
ent
and
297m
m2
afte
r (a
red
uctio
n of
70%
, 95%
CI 6
1% t
o 80
%). T
here
was
no
stat
istic
ally
sig
nific
ant
diffe
renc
e in
red
uctio
n of
lesi
onal
are
a be
twee
n PD
T a
nd 5
-FU
at
6 m
th (p
= 0
.72)
. No
patie
nts
wer
e co
mpl
etel
y cl
eare
d of
AK
s w
ith e
ither
tre
atm
ent
QoL
and
ret
urn
to n
orm
al a
ctiv
ity
Not
ass
esse
dA
Es A
ll pa
tient
s ex
peri
ence
d m
ild t
o m
oder
ate
pain
at
PDT
si
tes.
In w
k 1,
PD
T s
ites
wer
e si
gnifi
cant
ly m
ore
pain
ful t
han
5-FU
site
s, bu
t th
is d
iffer
ence
was
abs
ent
in w
k 2
and
reve
rsed
in
wk
4. T
here
was
no
sign
ifica
nt d
iffer
ence
bet
wee
n tr
eatm
ents
ov
eral
l ove
r th
e 4-
wk
peri
od. D
aily
sym
ptom
dia
ries
wer
e co
mpl
eted
by
11 p
atie
nts.
In w
k 1,
PD
T s
ites
wer
e si
gnifi
cant
ly
mor
e er
ythe
mat
ous
than
5-F
U s
ites
but
this
diff
eren
ce w
as
abse
nt in
wk
2 an
d re
vers
ed in
wk
3 an
d 4.
The
re w
as n
o si
gnifi
cant
diff
eren
ce b
etw
een
trea
tmen
ts o
vera
ll ov
er t
he
4-w
k pe
riod
. The
re w
as n
o bl
iste
ring
, ulc
erat
ion,
sca
rrin
g or
ph
otos
ensi
tivity
rea
ctio
n af
ter
eith
er t
reat
men
t m
etho
d. O
ne
patie
nt e
xper
ienc
ed c
onta
ct s
ensi
tivity
to
5-FU
Aut
hors
’ con
clus
ions
O
ne t
reat
men
t w
ith
PDT
usi
ng t
opic
al
5-A
LA a
ppea
rs t
o be
as
effe
ctiv
e an
d w
ell
tole
rate
d as
3 w
k of
tw
ice-
daily
top
ical
5-F
U,
a ch
eap
and
wid
ely
avai
labl
e al
tern
ativ
eA
ppra
isal
Thi
s st
udy
appe
ared
to
be
too
smal
l to
dete
ct
sign
ifica
nt t
reat
men
t ef
fect
s. T
he m
etho
ds
and
resu
lts w
ere
not
clea
rly
repo
rted
and
m
easu
res
to r
educ
e bi
as (
e.g.
rand
omis
atio
n,
blin
ding
and
allo
catio
n co
ncea
lmen
t) w
ere
not
repo
rted
at
all
so t
he r
elia
bilit
y of
th
e co
nclu
sion
s is
qu
estio
nabl
e
Appendix 13
200
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
201Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Leg
at e
t al. (
2006
)36
Dat
a so
urce
Abs
trac
tC
ount
ry A
ustr
iaLa
ngua
ge E
nglis
hSt
udy
desi
gn R
CT
No.
of p
arti
cipa
nts
Tota
l: 22
(m
ean
num
ber A
Ks
47,
rang
e 17
–89)
Inte
rven
tion:
22
(no.
of A
K n
ot
repo
rted
)C
ompa
rato
r: 22
(no
. of A
K n
ot
repo
rted
)2n
d C
ompa
rato
r: si
x (n
o. o
f AK
no
t re
port
ed)
No.
of r
ecru
itin
g ce
ntre
s N
ot s
tate
dFo
llow
-up
peri
od a
nd
freq
uenc
y FU
at
4, 1
2 an
d 24
wk
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
lesi
on a
nd
hist
olog
y A
KM
ain
elig
ibili
ty c
rite
ria
Not
sta
ted
Pati
ent
char
acte
rist
ics
% M
ale:
100
Age
ran
ge: 5
9–84
yrM
edia
n ag
e: 75
yrPa
tient
s ha
d m
ultip
le A
Ks
Con
com
itan
t tr
eatm
ent
Not
sta
ted
Tria
l tre
atm
ents
PD
T w
ith fr
actio
nate
d ill
umin
atio
n vs
PD
T w
ith u
nfra
ctio
nate
d ill
umin
atio
n. W
ithin
-par
ticip
ant
com
pari
son,
bu
t si
x pa
tient
s ha
d PD
T w
ith fr
actio
nate
d ill
umin
atio
n vs
alte
rnat
ive
frac
tiona
ted
illum
inat
ion,
due
to
seve
re p
ain
afte
r 1s
t fr
actio
nate
d do
seIn
terv
enti
on P
DT
with
unf
ract
iona
ted
illum
inat
ion:
Fol
low
ing
appl
icat
ion
of M
AL
crea
m fo
r 3
hr, r
ed li
ght
illum
inat
ion
(pea
k em
issi
on 6
35 n
m)
of a
sin
gle
dose
of 3
7 J/c
m2
was
app
lied
Com
para
tor
PDT
with
frac
tiona
ted
illum
inat
ion:
As
for
PDT
with
unf
ract
iona
ted
illum
inat
ion
exce
pt P
DT
was
giv
en in
tw
o do
ses
of 1
8.5
J/cm
2 div
ided
by
a da
rk in
terv
al
of 1
5 m
in2n
d co
mpa
rato
r PD
T w
ith a
ltern
ativ
e fr
actio
nate
d ill
umin
atio
n: A
s fo
r PD
T w
ith
unfr
actio
nate
d ill
umin
atio
n ex
cept
with
thr
ee
dose
s of
12.
3 J/c
m2 ,
with
tw
o da
rk in
terv
als
of
5 m
in
Mor
bidi
ty T
he m
ean
num
ber
of A
K
at w
k 4,
12
and
24 w
as r
educ
ed b
y 65
, 60
and
48%
with
unf
ract
iona
ted
PDT
and
56,
53,
and
50%
with
fr
actio
nate
d PD
T r
espe
ctiv
ely
(diff
eren
ce n
ot s
igni
fican
t, n =
14)
. Si
mila
r re
sults
see
n fo
r al
tern
ativ
e fr
actio
nate
d PD
T g
roup
QoL
and
ret
urn
to n
orm
al
acti
vity
Not
ass
esse
dA
Es
PDT
indu
ced
pain
(VA
S sc
ore)
w
as 6
.7 (
SE 0
.5)
for
unfr
actio
nate
d PD
T a
nd 6
.0 (
0.5)
for
frac
tiona
ted
PDT
(n =
14,
p =
0.0
2). T
here
was
no
sig
nific
ant
diffe
renc
e in
pai
n be
twee
n fr
actio
nate
d an
d al
tern
ativ
e fr
actio
nate
d pa
tient
s [8
.0 (
0.7)
vs
8.2
(0.3
) re
spec
tivel
y]
Aut
hors
’ con
clus
ions
PD
T w
ith fr
actio
nate
d an
d un
frac
tiona
ted
illum
inat
ion
wer
e si
mila
rly
effe
ctiv
e in
re
duci
ng A
Ks.
How
ever
, pai
n se
nsat
ion
duri
ng P
DT
was
si
gnifi
cant
ly le
ss in
tens
e w
ith
stan
dard
frac
tiona
ted
than
un
frac
tiona
ted
illum
inat
ion
Bri
ef s
tudy
app
rais
al F
ew
met
hodo
logi
cal d
etai
ls w
ere
prov
ided
in t
he a
bstr
act
and
the
resu
lts o
f thi
s sm
all s
tudy
m
ay n
ot b
e ge
nera
lisab
le
Appendix 13
200
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
201Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Mol
oney
et a
l. (2
007)
37
Dat
a so
urce
Abs
trac
tC
ount
ry N
ot s
tate
dLa
ngua
ge E
nglis
hSt
udy
desi
gn R
CT
No.
of p
arti
cipa
nts
Tota
l: 16
Inte
rven
tion:
16
Com
para
tor:
16N
o. o
f rec
ruit
ing
cent
res
Not
sta
ted
Follo
w-u
p pe
riod
and
fr
eque
ncy
1 m
th
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
lesi
on
and
hist
olog
y A
KM
ain
elig
ibili
ty
crit
eria
Not
sta
ted
Pati
ent
char
acte
rist
ics
% M
ale:
100
Age
ran
ge: 5
9–87
yrA
ll pa
tient
s ha
d A
Ks
on t
he s
calp
Con
com
itan
t tr
eatm
ent
Not
st
ated
Tria
l tre
atm
ents
MA
L–PD
T v
s ALA
–PD
TIn
terv
enti
on M
AL–
PDT:
MA
L cr
eam
w
as a
pplie
d fo
r 3
hr. F
urth
er P
DT
pa
ram
eter
s w
ere
not
repo
rted
Com
para
tor A
LA–P
DT:
20%
ALA
cr
eam
was
app
lied
for
5 hr
. Fur
ther
PD
T
para
met
ers
wer
e no
t re
port
ed
Mor
bidi
ty A
K c
ount
s re
duce
d by
5.
6 ±
3.2
(MA
L) v
s 6.
2 ±
1.9
(ALA
) (p
= 0
.588
) (n
= 1
5)Q
oL a
nd r
etur
n to
nor
mal
act
ivit
y N
ot a
sses
sed
AE
s All
patie
nts
(n =
15)
exp
erie
nced
pa
in, w
hich
was
of g
reat
er in
tens
ity o
n th
e A
LA t
reat
ed s
ide
at a
ll tim
e po
ints
: 3
min
, p =
0.1
51; 6
min
, p =
0.0
85; 1
2 m
in,
p =
0.01
2; 1
6 m
in, p
= 0
.029
. The
re w
as
also
long
er d
urat
ion
of d
isco
mfo
rt p
ost
trea
tmen
t w
ith A
LA (
p =
0.04
4)
Aut
hors
’ con
clus
ions
Bot
h A
LA a
nd
MA
L–PD
T r
esul
t in
sig
nific
ant
redu
ctio
n in
sca
lp A
Ks.
The
re is
no
sign
ifica
nt
diffe
renc
e in
effi
cacy
. How
ever
, ALA
is
mor
e pa
infu
l tha
n M
AL–
PDT
in t
he
trea
tmen
t of
ext
ensi
ve s
calp
AK
sB
rief
stu
dy a
ppra
isal
The
abs
trac
t pr
ovid
ed fe
w m
etho
dolo
gica
l det
ails
an
d in
volv
ed a
sm
all s
ampl
e, fo
llow
ed u
p fo
r on
ly 1
mth
, so
the
relia
bilit
y of
the
co
nclu
sion
s is
unc
lear
Appendix 13
202
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
203Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Mor
ton
et a
l. (20
06)48
Link
ed
publ
icat
ions
167,
168
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ries
Ir
elan
d, U
KLa
ngua
ge E
nglis
hSt
udy
desi
gn
RC
TN
o. o
f pa
rtic
ipan
tsTo
tal:
119
(150
1 le
sion
s)In
terv
entio
n: 1
19
(758
lesi
ons)
C
ompa
rato
r: 11
9 (7
43 le
sion
s)N
o. o
f re
crui
ting
ce
ntre
s 25
Follo
w-u
p pe
riod
and
fr
eque
ncy
FU
at w
k 12
and
24
. Add
ition
al
tele
phon
e FU
was
pe
rfor
med
at
wk
1 an
d 13
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
lesi
on
and
hist
olog
y N
on-
hype
rker
atot
ic A
KM
ain
elig
ibili
ty c
rite
ria
Mal
es a
nd fe
mal
es o
ver
18 yr
(16
yr in
Sco
tland
) w
ith c
linic
al d
iagn
osis
of
(at
leas
t th
ree)
non
-hy
perk
erat
otic
AK
on
the
face
and
/or
scal
p (o
f sim
ilar
seve
rity
and
nu
mbe
r on
bot
h si
des)
w
ere
elig
ible
for
incl
usio
n.
Patie
nts
that
rec
eive
d to
pica
l tre
atm
ent
with
in
the
prev
ious
3 m
th, r
egul
ar
UV
the
rapy
, pat
ient
s w
ith t
hick
or
pigm
ente
d le
sion
s or
por
phyr
ia w
ere
excl
uded
Pati
ent
char
acte
rist
ics
% M
ale:
91A
ge r
ange
: 54–
93 yr
Mea
n ag
e: 75
yrM
ean
no. o
f les
ions
per
si
de: s
ixM
edia
n le
sion
dia
met
er:
7 m
mFu
rthe
r pa
tient
ch
arac
teri
stic
s w
ere
repo
rted
Con
com
itan
t tr
eatm
ent
Not
sta
ted
Tria
l tre
atm
ents
MA
L–PD
T v
s cr
yoth
erap
y (w
ithin
-par
ticip
ant
com
pari
son)
Inte
rven
tion
MA
L–PD
T: A
fter
scra
ping
of
lesi
ons,
a 1-
mm
laye
r of
M
AL
160
mg/
g cr
eam
was
ap
plie
d (in
clud
ing
5 m
m
of s
urro
undi
ng t
issu
e) fo
r 3
hr (
unde
r oc
clus
ion)
. Fo
llow
ing
salin
e cl
eans
ing,
lesi
ons
wer
e ill
umin
ated
w
ith n
arro
wba
nd li
ght
(app
roxi
mat
ely
630
nm,
dose
37
J/cm
2 ) u
sing
a
stan
dard
LED
ligh
t so
urce
. Mea
n ill
umin
atio
n tim
e w
as 8
min
41
s. Le
sion
s w
ith a
non
-CR
w
ere
re-t
reat
ed a
t 12
wk
Com
para
tor
Dou
ble
free
ze–t
haw
cry
othe
rapy
: Li
quid
nitr
ogen
spr
ay
appl
ied
to a
chie
ve a
1-
to
2-m
m fr
ozen
rim
aro
und
the
mar
ked
outli
ne o
f th
e le
sion
. Mea
n fr
eezi
ng
time
was
16
s (±
7 s)
Mor
bidi
ty A
t w
k 12
lesi
on r
educ
tion
with
MA
L–PD
T w
as 8
7%
vs 7
6% (p
< 0
.001
). R
educ
tion
in le
sion
cou
nt a
t w
k 24
was
89%
w
ith M
AL–
PDT
vs
86%
with
cry
othe
rapy
(p
= 0.
2, n
= 1
08).
At
wk
12 C
R w
as 8
3% w
ith M
AL–
PDT
vs
72%
with
cry
othe
rapy
. At
wk
24 it
was
86%
(65
0/75
8) w
ith M
AL–
PDT
vs
83%
(61
3/74
3)
with
cry
othe
rapy
. 21%
of l
esio
ns w
ith C
R a
t w
k 24
had
nee
ded
re-t
reat
men
t w
ith c
ryot
hera
py a
t w
k 12
vs
10%
with
MA
L–PD
T, re
sults
wer
e in
depe
nden
t of
initi
al s
ever
ity g
rade
or
loca
tion
(ITT
po
pula
tion)
QoL
and
ret
urn
to n
orm
al a
ctiv
ity
Ove
rall
part
icip
ant
pref
eren
ce (
i.e. c
osm
etic
out
com
e, e
ffica
cy, a
nd s
kin
disc
omfo
rt)
was
49%
for
MA
L–PD
T v
s 21
% fo
r cr
yoth
erap
y (p
< 0
.001
, IT
T
anal
ysis
). R
esul
ts r
epor
ted
for
per-
prot
ocol
pop
ulat
ion
wer
e 45
%
vs 1
0%, p
< 0
.001
. Inv
estig
ator
pre
fere
nce
for
cosm
etic
out
com
e w
as 4
3% fo
r M
AL–
PDT
vs
12%
for
cryo
ther
apy,
p <
0.00
1, a
nd
for
over
all p
refe
renc
e w
as 5
2% v
s 16
%, p
< 0
.001
. Mos
t su
bjec
ts
wer
e ‘s
atis
fied’
to
‘ver
y sa
tisfie
d’ w
ith M
AL–
PDT
(co
mpa
red
with
cry
othe
rapy
and
pre
viou
s ot
her A
K t
reat
men
ts)
for
7/11
qu
estio
ns o
f a s
atis
fact
ion
ques
tionn
aire
. Mor
e th
an 9
0% w
ere
satis
fied
with
MA
L–PD
T in
ter
ms
of e
ffect
iven
ess
of t
reat
men
t, sc
arri
ng, s
kin
colo
ur a
nd a
ppea
ranc
e at
1-
and
3-m
th F
U.
Cry
othe
rapy
was
pre
ferr
ed fo
r tim
e ta
ken
over
tre
atm
ent
(92%
) co
mpa
red
to 7
8% fo
r M
AL–
PDT.
65%
wou
ld p
refe
r to
be
re-
trea
ted
with
MA
L–PD
T v
s 32
% w
ith c
ryot
hera
py (
n = 1
08)
AE
s Sk
in d
isco
mfo
rt V
AS
scor
es (
mea
n) w
ere
5.2
with
MA
L–PD
T v
s 4.
9 w
ith c
ryot
hera
py (
p =
0.24
) af
ter
1st
trea
tmen
t. Fo
r re
-tre
ated
lesi
ons,
mea
n VA
S sc
ores
wer
e 3.
7 vs
4.4
. Pat
ient
s pr
efer
red
cryo
ther
apy
in t
erm
s of
ski
n di
scom
fort
afte
r 1s
t tr
eatm
ent
(45%
vs
33%
, no
pref
eren
ce 2
2%, p
= 0
.07)
, but
the
re
was
no
diffe
renc
e fo
r re
-tre
ated
lesi
ons.
Skin
-rel
ated
AEs
wer
e re
port
ed b
y 62
% M
AL–
PDT
pat
ient
s vs
72%
for
cryo
ther
apy.
The
re w
as o
ne d
isco
ntin
uatio
n w
ith M
AL–
PDT
due
to
a lo
cal
reac
tion.
Mos
t sk
in-r
elat
ed A
Es w
ere
mild
to
mod
erat
e an
d tr
ansi
ent
Aut
hors
’ con
clus
ions
Whe
n tr
eate
d w
ith b
oth
MA
L–PD
T a
nd
cryo
ther
apy,
patie
nts
sign
ifica
ntly
pr
efer
MA
L–PD
T t
reat
men
t fo
r A
K. M
AL–
PDT
is a
n at
trac
tive
trea
tmen
t op
tion
for A
K, w
ith
com
para
ble
effic
acy
and
supe
rior
co
smet
ic o
utco
mes
com
pare
d w
ith
doub
le fr
eeze
–tha
w c
ryot
hera
pyB
rief
stu
dy a
ppra
isal
Thi
s st
udy
was
gen
eral
ly w
ell c
ondu
cted
and
re
port
ed; h
owev
er, i
t w
as a
n op
en-
labe
l tri
al, w
hich
can
lead
to
bias
in
favo
ur o
f a p
artic
ular
tre
atm
ent.
The
pos
sibi
lity
of in
stitu
tiona
l di
ffere
nces
and
/or
prot
ocol
de
viat
ion
(25
cent
res
in t
wo
coun
trie
s) a
ffect
ing
the
relia
bilit
y of
res
ults
was
illu
stra
ted
by t
he
vari
atio
n of
free
zing
tim
es u
sed
for
cryo
ther
apy
UV,
ultr
avio
let.
Appendix 13
202
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
203Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Par
iser
et a
l. (2
003)
49
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry U
SALa
ngua
ge E
nglis
hSt
udy
desi
gn R
CT
No.
of p
arti
cipa
nts
Tota
l: 80
(50
2 le
sion
s)In
terv
entio
n 42
(26
0 le
sion
)C
ompa
rato
r: 38
(24
2 le
sion
s)N
o. o
f rec
ruit
ing
cent
res
Five
Follo
w-u
p pe
riod
and
fr
eque
ncy
FU w
as a
t 3
mth
. AEs
wer
e as
sess
ed
duri
ng, i
mm
edia
tely
af
ter
PDT,
at w
k 2
and
3 m
th a
fter
the
2nd
PDT
tr
eatm
ent
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
lesi
on a
nd
hist
olog
y M
ild a
nd m
oder
ate
AK
Mai
n el
igib
ility
cri
teri
a M
ales
and
fem
ales
ove
r 18
yr w
ith 4
–10
prev
ious
ly
untr
eate
d m
ild t
o m
oder
ate
non-
pigm
ente
d A
K o
n th
e fa
ce a
nd s
calp
(at
leas
t 3
mm
di
amet
er)
wer
e el
igib
le fo
r in
clus
ion.
Fur
ther
elig
ibili
ty
crite
ria
wer
e re
port
edPa
tien
t ch
arac
teri
stic
s %
M
ale:
88A
ge r
ange
: 31–
84 yr
Mea
n ag
e: M
AL–
PDT
64;
pl
aceb
o PD
T 6
7T
he m
ajor
ity o
f les
ions
w
ere
mild
and
loca
ted
on
the
face
. Mos
t pa
tient
s w
ere
Fitz
patr
ick
skin
typ
e I o
r II
Con
com
itan
t tr
eatm
ent
Not
sta
ted
Tria
l tre
atm
ents
MA
L–PD
T
vs P
DT
with
pla
cebo
cre
amIn
terv
enti
on M
AL–
PDT:
Sc
ales
and
cru
sts
wer
e re
mov
ed u
sing
a c
uret
te M
AL
crea
m (
160
mg/
g) w
as a
pplie
d (1
-mm
thi
ckne
ss a
nd 5
mm
ar
ound
lesi
on)
for
mea
n 3
hr
unde
r oc
clus
ion.
Cre
am w
as
was
hed
off u
sing
a 0
.9%
sal
ine
solu
tion,
the
n a
non-
cohe
rent
re
d lig
ht w
as a
pplie
d: 5
70–
670
nm, d
ose
75 J/
cm2 ,
mea
n in
tens
ity 1
55 m
W/c
m2 (
rang
e 50
–200
mW
/cm
2 ). T
reat
men
t w
as r
epea
ted
afte
r 1
wk
Com
para
tor
PDT
with
pl
aceb
o cr
eam
: As
for
MA
L–PD
T b
ut w
ith p
lace
bo c
ream
Mor
bidi
ty F
or t
he M
AL–
PDT
gro
up, p
atie
nt r
espo
nse
was
32/
39 (
82%
) vs
8/3
8(21
%)
in p
lace
bo, t
reat
men
t di
ffere
nce
–61%
(p
= 0.
001)
For
the
MA
L–PD
T g
roup
le
sion
res
pons
e ra
te w
as 2
09/2
36 (
89%
) vs
92/
241
(38%
) fo
r pl
aceb
o. R
espo
nse
rate
was
sim
ilar
for
mild
an
d m
oder
ate
lesi
ons
in t
he M
AL
grou
p (9
0% a
nd 8
4%,
resp
ectiv
ely)
; pla
cebo
res
pons
e w
as h
ighe
r in
the
mild
le
sion
s (4
4% a
nd 2
5%)
QoL
and
ret
urn
to n
orm
al a
ctiv
ity
Inve
stig
ator
as
sess
ed c
osm
etic
out
com
e in
the
MA
L–PD
T g
roup
w
as ‘e
xcel
lent
’ or ‘
good
’ in
31/3
2 (9
7%)
patie
nts
and
whe
n as
sess
ed b
y pa
tient
s th
is w
as 2
9/32
(91
%). T
he
outc
ome
was
not
rat
ed ‘p
oor’
by
eith
er in
vest
igat
or
or p
atie
nt. 7
3% o
f 32
patie
nts
pref
erre
d M
AL–
PDT
to
prev
ious
tre
atm
ents
(5-
FU, c
ryot
hera
py, s
urge
ry)
AE
s 38
(90
%)
MA
L–PD
T p
atie
nts
had
an A
E vs
22
(58%
) in
pla
cebo
. One
MA
L–PD
T p
atie
nt d
isco
ntin
ued
due
to A
E. C
omm
on lo
cal A
Es w
ere:
burn
ing
sens
atio
n of
the
ski
n (2
7 M
AL
patie
nts
vs 4
); er
ythe
ma
(22
vs 8
); cr
ustin
g (1
6 vs
6);
pain
on
the
skin
(10
vs
0); b
liste
rs (
8 vs
2);
skin
oed
ema
(6 v
s 1)
; stin
ging
ski
n (6
vs
1) a
nd
skin
ulc
erat
ion
(5 v
s 0)
. Mor
e de
tails
in p
aper
Aut
hors
’ con
clus
ions
PD
T
usin
g to
pica
l MA
L w
as a
saf
e an
d ef
fect
ive
trea
tmen
t fo
r A
K w
ith e
xcel
lent
cos
met
ic
outc
ome.
It is
a p
rom
isin
g tr
eatm
ent
that
cou
ld b
enefi
t fr
om fu
rthe
r st
udy
Bri
ef s
tudy
app
rais
al
Thi
s st
udy
appe
ared
to
be
gene
rally
wel
l con
duct
ed
Appendix 13
204
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
205Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Par
iser
et a
l. (2
008)
56
Link
ed p
ublic
atio
ns16
9
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry U
SALa
ngua
ge E
nglis
hSt
udy
desi
gn R
CT
No.
of p
arti
cipa
nts
Tota
l: 10
0 (7
23 le
sion
s)
(four
pat
ient
s w
ere
trea
ted
as ‘t
rain
ing’
po
pula
tion)
Inte
rven
tion:
49
(363
le
sion
s)C
ompa
rato
r: 47
(36
0 le
sion
s)N
o. o
f rec
ruit
ing
cent
res
Eigh
tFo
llow
-up
peri
od
and
freq
uenc
y FU
3 m
th a
fter
last
tr
eatm
ent
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
lesi
on a
nd h
isto
logy
AK
Mai
n el
igib
ility
cri
teri
a Pr
evio
usly
un
trea
ted
mal
es a
nd n
on-p
regn
ant/
non-
lact
atin
g fe
mal
es w
ith a
dequ
ate
cont
race
ptio
n du
ring
and
1 m
th a
fter
trea
tmen
t th
at w
ere
at le
ast
18 yr
old
with
4–
10 n
on-p
igm
ente
d, n
on-h
yper
kera
totic
gr
ade
I or
II le
sion
s on
the
face
and
sca
lp
(at
leas
t 3-
mm
dia
met
er)
wer
e el
igib
le
for
incl
usio
n. E
xclu
sion
cri
teri
a w
ere
exte
nsiv
e bu
t in
clud
ed: i
mm
unos
uppr
essi
on,
porp
hyri
a, al
lerg
y to
MA
L or
sim
ilar,
alle
rgy
to n
ut p
rodu
cts
or p
rote
in a
ntig
ens,
regu
lar
UV
the
rapy
or
trea
tmen
t of
face
and
sca
lp
with
loca
l the
rapy
in p
revi
ous
30 d
, top
ical
th
erap
y in
pre
viou
s 3
mth
Pati
ent
char
acte
rist
ics
% M
ale:
82M
ean
age:
MA
L–PD
T 6
6.1;
Pla
cebo
PD
T
66.7
Age
ran
ge: 4
3–89
yrSk
in t
ype:
I 23%
; II 5
0%; I
II/IV
27%
Gra
de o
f les
ions
: Gra
de I
73%
; gra
de II
27%
The
maj
ority
of l
esio
ns w
ere
thin
(gr
ade
I) an
d lo
cate
d on
the
face
. Abo
ut 5
0% o
f pa
tient
s ha
d be
twee
n 8
and
10 le
sion
s in
to
tal
Con
com
itan
t tr
eatm
ent
Not
sta
ted
Tria
l tre
atm
ents
MA
L–PD
T v
s Pl
aceb
o PD
TIn
terv
enti
on M
AL–
PDT:
Pr
epar
atio
n of
lesi
ons
by
rem
oval
of s
cale
s an
d cr
usts
by
der
mal
cur
ette
, the
n ap
plic
atio
n of
1-m
m-t
hick
M
AL
crea
m t
o le
sion
and
su
rrou
ndin
g 5
mm
ski
n.
Occ
lusi
ve d
ress
ing
appl
ied
for
at le
ast
3 hr
(pe
rmitt
ed r
ange
2.
5–4
hr)
and
avoi
danc
e of
ex
posu
re t
o su
nlig
ht, b
righ
t in
door
ligh
t an
d ex
trem
e co
ld. A
rea
then
illu
min
ated
(a
vera
ge d
urat
ion,
8 m
in)
with
red
LED
(to
tal d
ose
37 J/
cm2 ,
5–8
cm fr
om s
kin)
. T
his
proc
edur
e w
as r
epea
ted
afte
r 1
wk
Com
para
tor
Plac
ebo
PDT:
A
s fo
r M
AL–
PDT
but
with
pl
aceb
o cr
eam
Mor
bidi
ty L
esio
n C
R r
ate
was
86%
fo
r M
AL–
PDT
vs
52%
for
plac
ebo,
OR
6.
9 (9
5% C
I 4.7
to
10.3
, p <
0.0
001)
. Pa
tient
CR
rat
e w
as 5
9% (
29/4
9)
for
MA
L–PD
T v
s 15
% (
7/47
) fo
r pl
aceb
o, O
R 1
3.2
(95%
CI 4
.1 t
o 43
.1,
p <
0.00
01).
3 m
th a
fter
trea
tmen
t 31
%
(15/
49)
MA
L–PD
T p
atie
nts
had
42
new
lesi
ons
vs 2
6% (
12/4
7) p
lace
bo-
PDT
pat
ient
s w
ith 3
4 ne
w le
sion
s. Fo
ur M
AL–
PDT
pat
ient
s ha
d at
leas
t fiv
e ne
w le
sion
s vs
tw
o pl
aceb
o. In
the
M
AL–
PDT
gro
up 6
7% o
f new
lesi
ons
wer
e on
the
face
vs
50%
pla
cebo
(p
= 0
.16)
, no
diffe
renc
e be
twee
n lo
catio
n of
new
lesi
ons
(p =
0.1
6)Q
oL a
nd r
etur
n to
nor
mal
ac
tivi
ty N
ot a
sses
sed
AE
s Any
AE/
any
loca
l AE
was
re
port
ed b
y 98
% (
52/5
3) in
the
MA
L–PD
T g
roup
. 45%
(22
/47)
rep
orte
d an
y A
E in
pla
cebo
gro
up, 4
5% (
21/4
7)
repo
rted
any
loca
l AE.
In t
he M
AL
grou
p 32
% w
ere
mild
(vs
38%
), 49
%
wer
e m
oder
ate
(vs
6%)
and
17%
wer
e se
vere
(vs
0%
). C
omm
only
rep
orte
d lo
cal A
Es fo
r th
e M
AL–
PDT
(n =
53)
(v
s pl
aceb
o, n
= 4
7) p
atie
nts
wer
e: er
ythe
ma
(77
vs 1
5%),
skin
bur
ning
se
nsat
ion
(72
vs 1
1%),
pain
of s
kin
(60
vs 2
1%),
prur
itis
(23
vs 1
1%),
skin
oe
dem
a (2
8 vs
2%
), sc
ab (
26 v
s 0%
), sk
in d
isco
mfo
rt (
23 v
s 2%
), bl
iste
r (1
5 vs
0%
) an
d sk
in e
xfol
iatio
n (1
1 vs
4%
)
Aut
hors
’ con
clus
ions
Giv
en t
hat
MA
L–PD
T h
as p
rove
d ex
celle
nt
cosm
etic
out
com
es, s
uper
ior
to
conv
entio
nal t
hera
py, t
his
sugg
ests
a
role
for
MA
L–PD
T u
sing
a r
ed L
ED
light
sou
rce
in p
atie
nts
with
mul
tiple
(u
p to
eig
ht) A
K le
sion
sB
rief
stu
dy a
ppra
isal
Thi
s st
udy
appe
ared
to
be g
ener
ally
wel
l co
nduc
ted
and
expl
ored
cen
tre-
effe
cts
on t
he r
esul
ts, a
lthou
gh fu
rthe
r de
tails
of t
he P
DT
ligh
t tr
eatm
ent
wou
ld h
ave
been
use
ful
d, d
ay(s
).
Appendix 13
204
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
205
Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Pui
zina
-Ivic
et
al. (
2008
)57
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry C
roat
iaLa
ngua
ge E
nglis
hSt
udy
desi
gn R
CT
No.
of p
arti
cipa
nts
Tota
l: 36
Inte
rven
tion:
Fr
actio
nate
d ill
umin
atio
n: 1
6C
ompa
rato
r: Si
ngle
ill
umin
atio
n: 2
0N
o. o
f rec
ruit
ing
cent
res
One
Follo
w-u
p pe
riod
and
fr
eque
ncy
24 w
k
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
lesi
on a
nd
hist
olog
y A
KM
ain
elig
ibili
ty c
rite
ria
Prev
ious
his
tolo
gica
lly
confi
rmed
dia
gnos
is o
f AK
Pati
ent
char
acte
rist
ics
Not
sta
ted
Tria
l tre
atm
ents
ALA
–PD
T w
ith 1
6-hr
incu
batio
n an
d tw
o lig
ht fr
actio
ns v
s ALA
–PD
T w
ith 5
-hr
incu
batio
n an
d a
sing
le
illum
inat
ion
Inte
rven
tion
ALA
–PD
T w
ith 1
6-hr
incu
batio
n an
d tw
o lig
ht
frac
tions
: Thi
ck c
rust
s w
ere
1st
rem
oved
with
oin
tmen
ts
(and
wet
dre
ssin
gs).
Afte
r cl
eani
ng t
he a
rea
with
a s
alin
e so
lutio
n, t
he 2
0% A
LA c
ream
was
app
lied
to a
thi
ckne
ss o
f ap
prox
imat
ely
1 m
m, c
over
ing
the
trea
ted
area
, and
1 cm
of
the
sur
roun
ding
ski
n. T
he a
rea
was
cov
ered
by
occl
usiv
e dr
essi
ng. A
lum
iniu
m fo
il w
as p
lace
d on
top
in o
rder
to
prot
ect
skin
from
am
bien
t lig
ht. T
here
was
the
n a
16-h
r in
cuba
tion
peri
od b
efor
e re
d lig
ht (
635
nm)
was
app
lied.
The
to
tal o
f 100
J/cm
2 was
del
iver
ed in
2 d
oses
of 5
0 J/c
m2 w
ith
a flu
ence
inte
nsity
of 3
0 m
W/c
m2 . T
here
was
a 2
-hr
brea
k be
twee
n ill
umin
atio
ns. S
pray
ing
of w
ater
and
coo
ling
with
fa
n w
as c
arri
ed o
ut t
o m
inim
ise
pain
sen
satio
ns. A
fter
the
trea
tmen
ts s
unbl
ock
oint
men
ts w
ere
reco
mm
ende
d fo
r th
e ne
xt fe
w d
ays
in a
dditi
on t
o su
n pr
otec
tion
mea
sure
s. Bi
opsi
es
wer
e pe
rfor
med
24
wk
afte
r ill
umin
atio
n in
pat
ient
s w
ith
fluor
esce
nce
dete
cted
afte
r 4
hrC
ompa
rato
r PD
T w
ith 5
-hr
incu
batio
n w
ith A
LA c
ream
and
si
ngle
ligh
t fr
actio
n: P
repa
ratio
n fo
r ill
umin
atio
n w
as a
s fo
r th
e in
terv
entio
n gr
oup.
The
re w
as t
hen
a 5-
hr in
cuba
tion
peri
od
befo
re r
ed li
ght
(635
nm
) w
as a
pplie
d. 1
00 J/
cm2 w
as d
eliv
ered
in
1 d
ose,
with
a fl
uenc
e in
tens
ity o
f 30
mW
/cm
2 . Sp
rayi
ng o
f w
ater
and
coo
ling
with
fans
, and
sun
pro
tect
ion
mea
sure
s w
ere
as fo
r th
e in
terv
entio
n gr
oup.
Biop
sies
wer
e pe
rfor
med
24
wk
afte
r ill
umin
atio
n in
pat
ient
s w
hom
fluo
resc
ence
afte
r 3-
hr in
cuba
tion
with
ALA
was
det
ecte
d
Mor
bidi
ty A
t 24
wk,
resi
dual
tum
our
was
fo
und
in 1
5 of
20
(75%
) bi
opsi
ed p
atie
nts
in
the
sing
le il
lum
inat
ion,
sh
orte
r-in
cuba
tion
grou
p. Tr
eatm
ent
was
re
peat
ed. A
t 24
wk,
ther
e w
as p
ersi
sten
ce
of t
umou
r in
2 o
f 16
(13%
) bi
opsi
ed p
atie
nts
in t
he fr
actio
nate
d,
long
er-in
cuba
tion
grou
pQ
oL a
nd r
etur
n to
no
rmal
act
ivit
y N
ot
asse
ssed
AE
s N
ot a
sses
sed
Aut
hors
’ con
clus
ions
PD
T
deliv
ered
as
frac
tiona
ted
illum
inat
ion
with
16
hr o
f in
cuba
tion
sepa
rate
d by
a 2
-hr
dark
inte
rval
sig
nific
antly
impr
oves
th
erap
eutic
out
com
e in
tum
our
erad
icat
ion
Bri
ef s
tudy
app
rais
al T
his
tria
l had
onl
y a
smal
l num
ber
of p
atie
nts.
Proc
edur
es o
f ra
ndom
isat
ion
and
blin
ding
of
out
com
e as
sess
ors
wer
e un
clea
r. N
o pa
tient
det
ails
w
ere
prov
ided
. Alth
ough
the
gr
oup
rece
ivin
g fr
actio
nate
d ill
umin
atio
n ha
d be
tter
out
com
es,
the
rela
tive
cont
ribu
tion
of t
he
long
er in
cuba
tion
time
and
the
frac
tiona
ted
deliv
ery
are
uncl
ear.
It is
als
o un
clea
r if
ther
e w
ere
any
AEs
Appendix 13
206
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
207Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Sot
irio
u et
al
. (20
09)61
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry G
reec
eLa
ngua
ge E
nglis
hSt
udy
desi
gn R
CT
No.
of p
arti
cipa
nts
Tota
l 30
(256
le
sion
s)In
terv
entio
n 30
(13
3 le
sion
s)C
ompa
rato
r 30
(12
3 le
sion
s)N
o. o
f rec
ruit
ing
cent
res
Not
sta
ted
Follo
w-u
p pe
riod
an
d fr
eque
ncy
Follo
wed
up
at 1
an
d 6
mth
afte
r tr
eatm
ent;
if gi
ven
a 2n
d tr
eatm
ent
then
cy
cle
final
FU
was
at
6 m
th a
fter
last
tr
eatm
ent
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y N
on-
hype
rker
atot
ic A
KM
ain
elig
ibili
ty
crit
eria
Clin
ical
di
agno
sis
of n
on-
hype
rker
atot
ic g
rade
I (
mild
) an
d gr
ade
II (m
oder
ate)
AK
on
dors
a of
han
ds a
nd fo
rear
ms.
Each
pat
ient
req
uire
d to
hav
e at
leas
t th
ree
lesi
ons
of c
ompa
rabl
e se
veri
ty o
n ea
ch s
ide
of
body
(to
tal o
f six
lesi
ons
min
imum
). Ex
clus
ion
crite
ria
wer
e an
y ot
her
derm
atol
ogic
al
dise
ases
or
cond
ition
s in
tr
eatm
ent
area
or
with
in
3 cm
, top
ical
tre
atm
ents
fo
r AK
with
in p
revi
ous
2 m
th, a
nd a
ny in
vasi
ve
tum
ours
in t
he
trea
tmen
t ar
eaPa
tien
t ch
arac
teri
stic
s%
Mal
e: 83
Mea
n ag
e: 64
yrA
ge r
ange
: 49–
79 yr
Seve
rity
of l
esio
ns:
Gra
de I:
54%
(PD
T),
54%
(Im
iqui
mod
); gr
ade
II: 4
6% (
PDT
), 46
%
(Imiq
uim
od)
Con
com
itan
t tr
eatm
ent
Non
e
Tria
l tre
atm
ents
ALA
–PD
T
vs Im
iqui
mod
5%
intr
aind
ivid
ual
righ
t/le
ft co
mpa
riso
nIn
terv
enti
on A
LA–P
DT:
lesi
ons
prep
ared
by
rem
ovin
g cr
usts
and
cu
rett
age,
whe
re le
sion
s w
ere
not
prep
ared
the
se w
ere
all
grad
e I.
20%
5-A
LA c
ream
app
lied
to le
sion
s an
d 5-
mm
sur
roun
ding
sk
in a
nd le
ft fo
r 4
hr. I
llum
inat
ion
imm
edia
tely
follo
win
g re
mov
al o
f dr
essi
ng u
sing
non
-coh
eren
t re
d lig
ht s
ourc
e, li
ght
dose
75
J/cm
2 , an
d flu
ence
rat
e of
75
mW
/cm
2 . Pa
tient
s gi
ven
two
PDT
ses
sion
s on
sam
e da
y, 1s
t se
ssio
n ta
rget
ing
the
hand
and
low
er fo
rear
m,
2nd
trea
ting
uppe
r tw
o-th
irds
of t
he fo
rear
m. T
wo
com
plet
e PD
T t
reat
men
ts w
ere
deliv
ered
to
all
area
s 15
d a
part
. Pai
n m
anag
emen
t du
ring
tre
atm
ent
incl
uded
use
of a
fan
and/
or
cool
ing
spra
ysC
ompa
rato
r Im
iqui
mod
: tr
eatm
ent
base
d on
app
rove
d do
sage
reg
ime
for
the
head
. Pa
tient
s ap
plie
d 50
0 m
g of
im
iqui
mod
5%
cre
am d
aily
for
3 d/
wk
prio
r to
sle
ep, c
ream
le
ft on
ski
n fo
r at
leas
t 8
hr.
Thi
s tr
eatm
ent
cont
inue
d fo
r 4
wk
(cou
rse
1). F
ollo
win
g a
4-w
k po
st-t
reat
men
t pe
riod
fo
r ob
serv
atio
n, a
ny p
atie
nts
with
lesi
ons
rem
aini
ng r
epea
ted
the
proc
ess
for
a fu
rthe
r 4
wk
(cou
rse
2)
Mor
bidi
ty 1
mth
: PD
T C
R r
ates
wer
e si
gnifi
cant
ly b
ette
r ov
eral
l and
for
grad
e I a
nd g
rade
II le
sion
s. C
R fo
r PD
T
70%
(87
/124
) an
d 18
% (
21/1
15)
for
imiq
uim
od (
p <
0.05
). G
rade
I le
sion
CR
was
75%
for
PDT
(50
/67)
and
34%
(2
1/61
) fo
r im
iqui
mod
(p
< 0.
05).
Gra
de II
CR
for
PDT
w
as 6
5% (
37/5
7), n
o gr
ade
II le
sion
s ac
hiev
ed C
R w
ith
imiq
uim
od (
0/54
). 6
mth
: The
CR
was
65%
(81
/124
) fo
r PD
T a
nd 5
6% (
64/1
15)
for
imiq
uim
od, b
ut t
he d
iffer
ence
w
as n
ot s
tatis
tical
ly s
igni
fican
t (p
> 0
.05)
. The
re w
as a
lso
no
sign
ifica
nt d
iffer
ence
for
grad
e I l
esio
ns, 7
2% (
48/6
7, P
DT
) vs
72%
(44
/61,
imiq
uim
od).
CR
wer
e si
gnifi
cant
ly h
ighe
r fo
r gr
ade
II le
sion
s in
the
PD
T t
reat
men
t ar
eas
(58%
, 33/
57)
than
with
imiq
uim
od (
37%
, 20/
54, p
< 0
.05)
QoL
and
ret
urn
to n
orm
al a
ctiv
ity
Cos
met
ic o
utco
me
was
ass
esse
d by
the
inve
stig
ator
s 6
mth
afte
r tr
eatm
ent
acco
rdin
g to
sca
rrin
g, at
roph
y, er
ythe
ma
and
pigm
ent
chan
ge. O
utco
mes
wer
e gr
aded
as
exce
llent
, goo
d, fa
ir o
r po
or. N
o si
gnifi
cant
diff
eren
ces
betw
een
the
grou
ps w
ere
obse
rved
; exc
elle
nt o
utco
mes
wer
e 85
% in
PD
T a
nd 7
5%
for
imiq
uim
od. A
pat
ient
-com
plet
ed q
uest
ionn
aire
at
6 m
th
asse
ssed
tre
atm
ent
pref
eren
ces.
The
PD
T p
roce
dure
was
pr
efer
red
by 6
9% o
f pat
ient
s, 55
% fa
vour
ed P
DT
in t
erm
s of
ef
ficac
y an
d 70
% w
ould
pre
fer
PDT
for
futu
re t
reat
men
tsA
Es
No
unex
pect
ed s
afet
y is
sues
wer
e re
cord
ed. P
DT
re
actio
ns d
urin
g tr
eatm
ent:
stin
ging
(83
%),
burn
ing
(100
%),
pain
(10
0%),
mod
erat
e er
ythe
ma
(100
%),
oede
ma
(67%
), bl
iste
ring
(27
%).
Rea
ctio
ns w
ere
wel
l tol
erat
ed, n
o fu
rthe
r tr
eatm
ent
was
req
uire
d an
d al
l res
olve
d w
ithin
7–1
5 d.
Im
iqui
mod
rea
ctio
ns w
ere
mos
t co
mm
only
app
licat
ion
site
rel
ated
: itc
hing
(21
%),
burn
ing
(11%
), pa
in (
4%).
Loca
l sk
in r
eact
ions
in t
he t
reat
men
t ar
ea w
ere
mos
tly m
ild t
o m
oder
ate
and
wel
l tol
erat
ed, a
nd m
ore
inte
nse
duri
ng
cour
se 1
tha
n co
urse
2: e
ryth
ema
(93%
), cr
ustin
g (1
1%),
scal
ing
(11%
), er
osio
ns/u
lcer
atio
ns (
7%),
oede
ma
(7%
)
Aut
hors
’ con
clus
ions
ALA
–PD
T a
nd im
iqui
mod
5%
cre
am
are
com
para
ble
trea
tmen
ts fo
r up
per
extr
emity
AK
. ALA
–PD
T
shou
ld b
e co
nsid
ered
as
a 1s
t-lin
e th
erap
y fo
r bo
th g
rade
I an
d gr
ade
II A
K o
f the
ext
rem
ities
Bri
ef s
tudy
app
rais
al A
lthou
gh
this
tri
al u
sed
an in
trai
ndiv
idua
l ra
ndom
isat
ion
desi
gn fo
r tr
eatm
ent,
it fa
iled
to r
epor
t on
as
pect
s of
met
hods
(in
clud
ing
rand
omis
atio
n) a
nd d
id n
ot u
se
an IT
T a
naly
sis
Out
com
e as
sess
ors
wer
e no
t bl
inde
d an
d on
ly in
vest
igat
or-
asse
ssed
cos
met
ic o
utco
mes
w
ere
repo
rted
. The
res
ults
su
gges
t th
ere
may
be
little
di
ffere
nce
betw
een
PDT
and
im
iqui
mod
for
grad
e I l
esio
ns, b
ut
PDT
may
be
bett
er fo
r gr
ade
IIT
hese
res
ults
can
be
cons
ider
ed
mod
erat
ely
relia
ble,
but
un
cert
aint
ies
do e
xist
abo
ut t
he
choi
ce o
f sta
tistic
al t
echn
ique
s us
ed, t
he in
cons
iste
nt r
epor
ting
of s
ome
resu
lts, a
nd t
he s
ampl
e si
ze (
as t
he a
utho
rs a
ssum
ed
that
lesi
ons
with
in p
atie
nts
wer
e in
depe
nden
t)
Appendix 13
206
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
207
Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Sm
ith e
t al.
(200
3)50
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry U
SALa
ngua
ge E
nglis
hSt
udy
desi
gn R
CT
No.
of
part
icip
ants
Tota
l: 36
Inte
rven
tion
12
(ALA
with
blu
e lig
ht)
Com
para
tor:
12
(ALA
with
lase
r lig
ht)
2nd
Com
para
tor:
12
(5-F
U)
No.
of r
ecru
itin
g ce
ntre
s N
ot s
tate
dFo
llow
-up
peri
od
and
freq
uenc
y FU
at
end
of t
reat
men
t, 2
wk
and
4 w
k
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
lesi
on a
nd
hist
olog
y A
KM
ain
elig
ibili
ty c
rite
ria
It ap
pear
ed t
hat
Cau
casi
an
patie
nts
with
a m
inim
um o
f fo
ur n
on-h
yper
kera
totic
AK
of
the
face
or
scal
p w
ere
elig
ible
for
incl
usio
nPa
tien
t ch
arac
teri
stic
s%
Mal
e: 81
Mea
n ag
e: A
LA w
ith b
lue
light
, 58.
9; A
LA w
ith la
ser
light
61.
0; 5
-FU
64.
3M
ean
no. o
f les
ions
: 6–7
per
pa
tient
Con
com
itan
t tr
eatm
ent
Patie
nts
with
mor
e dr
amat
ic
cuta
neou
s re
activ
ity (
6/11
5-
FU a
nd 1
/12
PDT-
lase
r pa
tient
s) w
ere
trea
ted
with
di
lute
ace
tic a
cid
soak
s an
d to
pica
l low
pot
ency
co
rtic
oste
roid
(2–
3 tim
es
daily
)
Tria
l tre
atm
ents
Bro
ad a
rea
ALA
–PD
T w
ith b
lue
light
vs
broa
d ar
ea A
LA–P
DT
with
la
ser
light
vs
5-FU
Inte
rven
tion
ALA
–PD
T
(blu
e lig
ht):
Follo
win
g to
pica
l ap
plic
atio
n of
ALA
for
1 hr
to
a br
oad
area
, illu
min
atio
n w
ith
blue
-ligh
t PD
T fo
r 10
00 s.
Tw
o tr
eatm
ents
30
d ap
art
wer
e ap
plie
dC
ompa
rato
r A
LA–P
DT
(w
ith la
ser)
: Fol
low
ing
broa
d ar
ea t
opic
al A
LA a
pplic
atio
n fo
r 1
hr, p
ulse
d dy
e la
ser
was
ad
min
iste
red
(595
nm
, 75
J/cm
2 w
ith 1
0-m
s pu
lse
dura
tion
usin
g a
10-m
m s
pot
size
, 10
% o
verl
ap o
f eac
h la
ser
impa
ct a
nd t
wo
pass
es a
cros
s tr
eatm
ent
area
). Pa
tient
s re
ceiv
ed t
wo
trea
tmen
ts 3
0 d
apar
t2n
d co
mpa
rato
r 5-
FU: 5
%
fluor
oura
cil c
ream
app
lied
once
or
twic
e da
ily fo
r 4
wk
Mor
bidi
ty 7
5% o
r m
ore
lesi
ons
wer
e cl
eare
d in
9/1
2 PD
T-bl
ue li
ght
patie
nts
vs 5
/12
PDT-
lase
r vs
9/1
1 5-
FU.
100%
of l
esio
ns w
ere
clea
red
in 6
/12
PDT-
blue
ligh
t pa
tient
s vs
1/1
2 PD
T-la
ser
vs 6
/11
5-FU
. The
cum
ulat
ive
clea
ranc
e ra
te (
or in
divi
dual
AK
lesi
on r
ate)
was
80%
(P
DT-
blue
ligh
t), 5
0% (
PDT-
lase
r) a
nd 7
9% (
5-FU
)Q
oL a
nd r
etur
n to
nor
mal
act
ivit
y A
ll th
ree
trea
tmen
ts s
how
ed im
prov
emen
t in
glo
bal r
espo
nse,
ta
ctile
rou
ghne
ss a
nd m
ottle
d hy
perp
igm
enta
tion;
th
e 5-
FU a
nd P
DT-
blue
ligh
t gr
oups
ten
ded
tow
ards
m
ore
bene
fit fo
r ta
ctile
rou
ghne
ss, w
here
as t
he 5
-FU
an
d PD
T-la
ser
grou
ps fa
vour
ed p
igm
enta
tion.
PD
T-bl
ue li
ght
was
the
onl
y gr
oup
in w
hich
the
sig
ns o
f ph
otoa
gein
g co
mpl
etel
y re
solv
ed b
ased
on
the
glob
al
resp
onse
sco
re (
two
patie
nts)
. Non
e of
the
tre
atm
ents
w
orse
ned
sign
s of
pho
toag
eing
AE
s Fo
ur P
DT-
blue
ligh
t an
d 3
PDT-
lase
r pa
tient
s re
port
ed m
ild o
r m
oder
ate
stin
ging
dire
ctly
afte
r th
erap
y bu
t no
t at
sub
sequ
ent
FU. E
ryth
ema
was
the
m
ost
pron
ounc
ed A
E; 5
-FU
pat
ient
s ha
d th
e gr
eate
st
aver
age
incr
ease
and
sho
wed
res
idua
l ery
them
a at
4
wk.
Cru
stin
g an
d er
osio
ns w
ere
only
see
n w
ith 5
-FU
. T
here
was
one
dis
cont
inua
tion
in t
he 5
-FU
gro
up d
ue
to a
sev
ere
confl
uent
ery
them
atou
s re
actio
n
Aut
hors
’ con
clus
ions
Bro
ad
area
PD
T t
reat
men
t w
ith A
LA p
lus
activ
atio
n w
ith b
lue
light
app
ears
to
be
as e
ffect
ive
as 5
-FU
in t
he
trea
tmen
t of
AK
. ALA
plu
s la
ser
light
is
som
ewha
t le
ss e
ffect
ive
than
the
ab
ove
ther
apie
sB
rief
stu
dy a
ppra
isal
Thi
s w
as a
sm
all s
tudy
with
poo
rly
repo
rted
m
etho
dolo
gy. A
dditi
onal
tre
atm
ent
was
giv
en t
o pa
tient
s th
at h
ad s
ever
e re
actio
ns, w
hich
may
hav
e be
en a
co
nfou
ndin
g fa
ctor
. The
rel
iabi
lity
of
the
resu
lts is
the
refo
re u
ncer
tain
Appendix 13
208
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
209Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Sze
imie
s et
al.
(200
7)38
Link
ed p
ublic
atio
ns17
0–17
3
Dat
a so
urce
Abs
trac
tC
ount
ry N
ot s
tate
dLa
ngua
ge E
nglis
hSt
udy
desi
gn R
CT
No.
of p
arti
cipa
nts
Tota
l: 25
(23
8 le
sion
s)In
terv
entio
n: N
ot s
tate
dC
ompa
rato
r: N
ot s
tate
dN
o. o
f rec
ruit
ing
cent
res
Not
sta
ted
Follo
w-u
p pe
riod
and
fr
eque
ncy
FU a
t 2
wk
and
3 m
th
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
lesi
on
and
hist
olog
y A
KM
ain
elig
ibili
ty
crit
eria
Not
sta
ted
Pati
ent
char
acte
rist
ics
% M
ale:
68M
ean
age:
73 yr
Con
com
itan
t tr
eatm
ent
Not
st
ated
Tria
l tre
atm
ents
MA
L–PD
T w
ith V
PL
vs M
AL–
PDT
with
LED
ligh
t (w
ithin
-pa
rtic
ipan
t co
mpa
riso
n)In
terv
enti
on P
DT-
VPL
: MA
L cr
eam
w
as a
pplie
d to
tar
get
area
for
3 hr
. One
si
de r
ecei
ved
VPL
at
80 J/
cm2 (
doub
le
puls
ed a
t 40
J/cm
2 ) w
ith a
pul
se t
rain
of
15
impu
lses
, eac
h of
5-m
s du
ratio
n,
usin
g a
610–
950
nm fi
ltere
d ha
nd p
iece
. T
he o
ppos
ite s
ide
rece
ived
LED
ligh
t (3
7 J/c
m2 f
or 1
2 m
in)
Com
para
tor
PDT-
LED
: See
abo
ve
Mor
bidi
ty In
filtr
atio
n an
d ke
rato
ses
scor
e: N
o si
gnifi
cant
di
ffere
nce
betw
een
LED
0.8
6 (0
.71)
and
VPL
1.0
5 (0
.74)
, p
= 0.
292
QoL
and
ret
urn
to n
orm
al
acti
vity
No
sign
ifica
nt d
iffer
ence
s in
pat
ient
sat
isfa
ctio
n be
twee
n tr
eatm
ents
(p
= 0.
425)
AE
s Pa
in a
sses
smen
t (V
AS)
im
med
iate
ly a
fter
PDT
sho
wed
si
gnifi
cant
ly lo
wer
pai
n le
vels
for
the
VPL
sid
e (4
.3 v
s 6.
4)
Aut
hors
’ con
clus
ions
The
use
of V
PL
is a
n ef
ficie
nt a
nd u
sefu
l alte
rnat
ive
in t
he
phot
odyn
amic
tre
atm
ent
of A
K, w
here
ot
herw
ise
pain
dev
elop
men
t ca
n be
a li
miti
ng
fact
or fo
r th
e pe
rfor
man
ce o
f PD
TB
rief
stu
dy a
ppra
isal
Min
imal
rep
ortin
g of
bo
th m
etho
ds a
nd r
esul
ts m
eans
litt
le c
an b
e de
duce
d fr
om t
his
conf
eren
ce a
bstr
act
VPL
, var
iabl
e pu
lsed
ligh
t.
Appendix 13
208
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
209Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Sze
imie
s et
al
. (20
02)51
Link
ed
publ
icat
ions
174,
175
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ries
Aus
tria
, G
erm
any,
Italy,
Sw
itzer
land
, the
N
ethe
rlan
dsLa
ngua
ge E
nglis
hSt
udy
desi
gn R
CT
No.
of p
arti
cipa
nts
Tota
l: 20
2 (7
32
lesi
ons)
Inte
rven
tion:
102
(3
84 le
sion
s)C
ompa
rato
r: 10
0 (3
48 le
sion
s)N
o. o
f rec
ruit
ing
cent
res
13Fo
llow
-up
peri
od
and
freq
uenc
y A
t 2
wk
and
3 m
th
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
lesi
on a
nd
hist
olog
y A
KM
ain
elig
ibili
ty c
rite
ria
Patie
nts
> 18
yr o
ld, w
ith u
p to
10
AK
lesi
ons
suita
ble
for
cryo
ther
apy
and
no t
reat
men
t w
ithin
the
last
4 w
k w
hen
elig
ible
. Dia
gnos
is w
as b
ased
on
clin
ical
ass
essm
ent
(and
hi
stol
ogy
whe
re n
eede
d).
Patie
nts
rece
ivin
g re
gula
r U
V t
hera
py a
nd p
atie
nts
with
pig
men
ted
lesi
ons
or
porp
hyri
a w
ere
excl
uded
Pati
ent
char
acte
rist
ics
% M
ale:
61A
ge r
ange
: 42–
89 yr
Mea
n ag
e: 71
yr (
PDT
), 72
yr
(cry
othe
rapy
)58
% o
f pat
ient
s ha
d 1–
3 le
sion
s, 33
% h
ad 4
–7 le
sion
s, an
d 9%
had
8–1
0 le
sion
s. Le
sion
s w
ere
mos
tly o
f thi
n (4
0%)
or m
oder
ate
(52%
) gr
ade,
and
mos
t w
ere
loca
ted
on t
he fa
ce (
63%
) or
sca
lp
(28%
)C
onco
mit
ant
trea
tmen
t N
ot s
tate
d
Tria
l tre
atm
ents
MA
L–PD
T v
s C
ryot
hera
pyIn
terv
enti
on M
AL–
PDT:
Loo
se
crus
ts w
ere
rem
oved
usi
ng a
cu
rett
e an
d th
e su
rfac
e ge
ntly
ro
ughe
ned.
MA
L cr
eam
(16
0 m
g/g)
w
as a
pplie
d as
a 1
-mm
-thi
ck la
yer
and
to 5
mm
of s
urro
undi
ng n
orm
al
tissu
e. T
he a
rea
was
cov
ered
with
an
occ
lusi
ve d
ress
ing
for
3 hr
, afte
r w
hich
the
cre
am w
as w
ashe
d of
f w
ith a
sal
ine
solu
tion,
follo
wed
by
illum
inat
ion
with
non
-coh
eren
t re
d lig
ht (
570–
670
nm)
with
a t
otal
lig
ht d
ose
of 7
5 J/c
m2 a
nd a
ligh
t in
tens
ity o
f 70–
200
mW
/cm
2 . The
m
ean
illum
inat
ion
time
was
11
min
. U
p to
10
lesi
ons
wer
e tr
eate
d at
th
e sa
me
sess
ion.
The
pro
cedu
re
was
rep
eate
d af
ter
1 w
k in
lesi
ons
not
on t
he fa
ce o
r sc
alp
(8%
of
patie
nts)
Com
para
tor
Cry
othe
rapy
: pr
epar
atio
n w
ith s
uper
ficia
l cu
rett
age,
follo
wed
by
cryo
ther
apy
with
liqu
id n
itrog
en s
pray
to
achi
eve
a 1-
to
2-m
m fr
ozen
rim
ou
tsid
e th
e m
arke
d le
sion
out
line.
T
he m
ean
tota
l fre
ezin
g tim
e w
as
24 s.
The
free
zing
pro
cedu
re w
as
perf
orm
ed in
tw
o cy
cles
dur
ing
the
sing
le t
reat
men
t se
ssio
n
Mor
bidi
ty T
he o
vera
ll C
R r
ate
was
69%
(25
2/36
7) fo
r PD
T v
s 75
%
(250
/332
) fo
r cr
yoth
erap
y. H
ighe
r re
spon
se r
ates
wer
e ob
serv
ed in
gra
de
I (th
in)
lesi
ons
than
in t
hick
er le
sion
s. G
rade
I fa
cial
lesi
ons
show
ed t
he b
est
resp
onse
reg
ardl
ess
of in
terv
entio
n ar
mQ
oL a
nd r
etur
n to
nor
mal
act
ivit
y C
osm
etic
out
com
e w
as s
igni
fican
tly
bett
er in
PD
T g
roup
(p
= 0.
035)
, whe
re
96%
of i
nves
tigat
ors
and
98%
of p
atie
nts
grad
ed o
utco
me
as e
xcel
lent
or
good
(v
s 81
% a
nd 9
1%, r
espe
ctiv
ely,
for
cryo
ther
apy
grou
p). I
n th
e PD
T g
roup
, of
the
43
prev
ious
ly t
reat
ed p
atie
nts
(var
ious
tre
atm
ents
suc
h as
cry
othe
rapy
an
d 5-
FU)
32 r
ated
PD
T a
s be
tter
, 10
as
equa
l, an
d on
e w
orse
tha
n th
e pr
evio
us
trea
tmen
tA
Es
Loca
l AEs
wer
e re
port
ed b
y 44
(4
3%)
of P
DT
pat
ient
s vs
26
(26%
) of
cr
yoth
erap
y pa
tient
s. T
he c
omm
ones
t w
ere
burn
ing
sens
atio
n (P
DT
32%
vs
cryo
ther
apy
9%),
skin
pai
n (1
0% v
s 13
%)
and
crus
ting
(5%
vs
6%). T
hree
pa
tient
s st
oppe
d tr
eatm
ent
due
to lo
cal
reac
tions
– o
ne P
DT
(bu
rnin
g) a
nd t
wo
cryo
ther
apy
(pai
n)
Aut
hors
’ con
clus
ions
PD
T fo
r tr
eatin
g A
K
has
a si
mila
r re
spon
se r
ate
to c
ryot
hera
py,
but
with
sup
erio
r co
smet
ic r
esul
ts a
nd h
igh
patie
nt s
atis
fact
ion
Bri
ef s
tudy
app
rais
al In
rel
atio
n to
CR
, th
e au
thor
s’ c
oncl
usio
ns a
ppea
red
only
to
rela
te t
o th
in fa
cial
lesi
ons,
with
unc
erta
inty
su
rrou
ndin
g ot
her
resu
lts (
whi
ch fr
eque
ntly
la
cked
p-v
alue
s). C
osm
etic
out
com
e an
d sa
tisfa
ctio
n re
sults
wer
e ba
sed
on s
mal
ler
patie
nt n
umbe
rs. T
he s
tudy
was
not
blin
ded
whi
ch c
oupl
ed w
ith t
he r
eal p
ossi
bilit
y of
inst
itutio
nal d
iffer
ence
s an
d pr
otoc
ol
devi
atio
n (1
3 ce
ntre
s in
five
cou
ntri
es)
cast
s fu
rthe
r do
ubt
on t
he r
elia
bilit
y of
the
res
ults
Appendix 13
210
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
211Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Sze
imie
s et
al. (
2009
)58
Link
ed
publ
icat
ions
169
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ries
G
erm
any,
USA
Lang
uage
Eng
lish
Stud
y de
sign
R
CT
No.
of
part
icip
ants
Tota
l: 13
1In
terv
entio
n:
57 (
plus
16
not
rand
omis
ed –
incl
uded
onl
y in
A
E an
alys
is)
Com
para
tor:
58N
o. o
f rec
ruit
ing
cent
res
10Fo
llow
-up
peri
od a
nd
freq
uenc
y FU
3
mth
afte
r la
st
trea
tmen
t
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
lesi
on a
nd h
isto
logy
A
KM
ain
elig
ibili
ty c
rite
ria
Mal
es a
nd
non-
preg
nant
, non
-lact
atin
g w
omen
ag
ed o
ver
18 yr
with
4–1
0 pr
evio
usly
un
trea
ted,
non
-pig
men
ted,
non
-hy
perk
erat
otic
gra
de I
or II
lesi
ons
on t
he fa
ce a
nd s
calp
(at
leas
t 3-
mm
di
amet
er)
wer
e el
igib
le fo
r in
clus
ion.
Ex
clus
ion
crite
ria
wer
e ex
tens
ive
and
incl
uded
: im
mun
osup
pres
sion
, po
rphy
ria,
alle
rgy
to M
AL
or s
imila
r, hy
pers
ensi
tivity
to
nut
prod
ucts
or
oth
er p
rote
in a
ntig
ens,
regu
lar
UV
tre
atm
ent
of fa
ce o
r sc
alp
in
prev
ious
30
d, t
opic
al t
hera
py in
pr
evio
us 3
mth
Pati
ent
char
acte
rist
ics
% M
ale:
79M
ean
age:
MA
L–PD
T 6
9.5;
Pla
cebo
PD
T 6
7.0
Age
ran
ge: 4
1–90
yr s
kin
type
: I
19%
; II 4
4%; I
II/IV
27%
; IV
10%
le
sion
s: gr
ade
I (th
in)
41%
; gra
de II
(m
oder
ate)
59%
The
maj
ority
of l
esio
ns w
ere
loca
ted
on t
he fa
ce o
r sc
alp,
patie
nts
had
a m
edia
n of
sev
en le
sion
s ea
ch a
nd
the
med
ian
max
imum
dia
met
er w
as
9 m
mC
onco
mit
ant
trea
tmen
t 22
pa
tient
s (1
4 M
AL,
8 p
lace
bo)
rece
ived
ora
l ana
lges
ic t
reat
men
t or
fe
ntan
yl p
atch
es
Tria
l tre
atm
ents
MA
L–PD
T v
s Pl
aceb
o PD
TIn
terv
enti
on M
AL–
PDT:
Afte
r de
brid
emen
t of
lesi
ons,
1-m
m-
thic
k M
AL
crea
m (
160
mg/
g)
was
app
lied
to e
ach
lesi
on a
nd
5-m
m s
urro
undi
ng s
kin
for
3 hr
(p
erm
itted
ran
ge 2
.5–4
hr)
und
er
occl
usio
n. L
esio
ns w
ere
clea
ned
with
a s
alin
e so
lutio
n, t
hen
illum
inat
ed w
ith n
on-c
oher
ent
LED
red
ligh
t (a
vera
ge d
urat
ion
9 m
in, m
ean
dose
37
J/cm
2 , m
ean
inte
nsity
74
mW
/cm
2 , ra
nge
56–
83 m
W/c
m2 )
with
the
ligh
t so
urce
ke
pt a
t 5–
8 cm
from
ski
n. B
reak
s in
illu
min
atio
n w
ere
allo
wed
pr
ovid
ed t
hat
trea
tmen
t w
as
com
plet
ed w
ithin
4 h
of o
cclu
sion
. T
his
proc
ess
was
rep
eate
d af
ter
1 w
kC
ompa
rato
r Pl
aceb
o PD
T: A
s fo
r M
AL–
PDT
but
with
pla
cebo
cr
eam
Mor
bidi
ty L
esio
n re
spon
se r
ate
was
83%
(34
8/41
8)
with
MA
L vs
29%
(11
9/41
4) fo
r pl
aceb
o, O
R 1
3.8
(9.5
to
19.9
, p <
0.0
01).
Patie
nt C
R r
ate
with
MA
L w
as 6
8% (
39/5
7) v
s 7%
(4/
59)
for
plac
ebo,
OR
39.
5 (1
0.5
to 1
49.2
, p <
0.0
01).
At
3 m
th a
fter
trea
tmen
t, de
velo
pmen
t of
new
lesi
ons
was
18%
(10
/56)
in
MA
L pa
tient
s vs
34%
(20
/58)
for
plac
ebo,
p =
0.0
4.
73%
wer
e on
the
sca
lp in
the
MA
L gr
oup
vs 5
9%.
Res
pons
e ra
tes
wer
e hi
gher
for
smal
l les
ions
(3
–10
mm
) on
the
face
but
bet
ter
for
larg
e le
sion
s (>
20
mm
) on
the
sca
lpQ
oL a
nd r
etur
n to
nor
mal
act
ivit
y N
ot a
sses
sed
AE
s 85
% (
62/7
3) M
AL
patie
nts
repo
rted
AEs
vs
60%
(3
5/58
) an
d m
ost
wer
e as
soci
ated
with
tre
atm
ent
site
(31
2/36
8 an
d 56
/89,
res
pect
ivel
y). T
he m
ost
com
mon
ly r
epor
ted
loca
l AEs
with
MA
L w
ere
pain
of
the
ski
n 55
% (
40/7
3) v
s 22
% (
13/5
8), e
ryth
ema
52%
(38
/73)
vs
5% (
3/58
), an
d sk
in b
urni
ng s
ensa
tion
36%
(26
/73)
vs
12%
(21
/58)
. In
the
plac
ebo
grou
p al
l but
six
loca
l AEs
wer
e m
ild; m
ost
MA
L A
Es w
ere
mild
to
mod
erat
e. N
inet
een
MA
L pa
tient
s ha
d se
vere
lo
cal A
Es c
onsi
dere
d tr
eatm
ent
rela
ted:
pai
n of
the
sk
in 1
3, e
ryth
ema
six,
ski
n bu
rnin
g se
nsat
ion
five,
sk
in e
xfol
iatio
n fo
ur, s
cab
one,
ski
n sw
ellin
g on
e an
d fa
ce s
wel
ling
one.
The
re w
ere
also
six
non
-loca
l AEs
: di
zzin
ess
and
incr
ease
d pe
rspi
ratio
n, e
yelid
oed
ema
(thr
ee r
epor
ts)
and
head
ache
(on
e re
port
). Tw
o M
AL
patie
nts
disc
ontin
ued
due
to s
ever
e sk
in p
ain
Aut
hors
’ con
clus
ions
To
pica
l MA
L–PD
T u
sing
an
LED
is a
n ef
fect
ive
trea
tmen
t fo
r m
ultip
le A
Ks
Bri
ef s
tudy
app
rais
al
Gen
eral
ly a
wel
l-con
duct
ed
tria
l tha
t co
nsid
ered
cen
tre
effe
cts
on t
he r
esul
ts;
how
ever
, a s
ubgr
oup
anal
ysis
of
pat
ient
s th
at r
ecei
ved
addi
tiona
l pai
nkill
ers
may
ha
ve b
een
usef
ul
Appendix 13
210
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
211Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Ta
rste
dt e
t al.
(200
5)52
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry S
wed
enLa
ngua
ge
Engl
ish
Stud
y de
sign
R
CT
No.
of
part
icip
ants
Tota
l: 21
1 (4
13
lesi
ons)
Inte
rven
tion:
105
(1
98 le
sion
s)C
ompa
rato
r: 10
6 (2
15 le
sion
s)N
o. o
f re
crui
ting
ce
ntre
s 21
Follo
w-u
p pe
riod
and
fr
eque
ncy
At
3 m
th
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
lesi
on a
nd h
isto
logy
A
K (
grad
e I o
r II)
Mai
n el
igib
ility
cri
teri
a Pa
tient
s ag
ed a
t le
ast
18 yr
with
up
to 1
0 cl
inic
ally
dia
gnos
ed A
K le
sion
s on
the
fa
ce a
nd/o
r sc
alp,
whi
ch w
ere
mild
(g
rade
I) o
r m
oder
ate
(gra
de II
) an
d no
n-pi
gmen
ted,
wer
e el
igib
lePa
tien
t ch
arac
teri
stic
s%
Mal
e: 39
Mea
n ag
e: 69
yr s
ingl
e-se
ssio
n gr
oup,
68 yr
2-s
essi
on g
roup
Aro
und
one-
half
of t
he p
atie
nts
had
rece
ived
pri
or t
reat
men
t fo
r AK
. M
ean
lesi
on d
iam
eter
was
aro
und
10 m
m. T
he m
ajor
ity o
f pat
ient
s (7
6–83
% in
bot
h gr
oups
) ha
d 1
or 2
le
sion
s, an
d 90
% o
f les
ions
wer
e on
th
e fa
ce, w
ith t
he r
est
bein
g on
the
sc
alp.
Furt
her
char
acte
rist
ics
wer
e re
port
edC
onco
mit
ant
trea
tmen
t Lo
cal
anae
sthe
tic if
nee
ded
duri
ng
trea
tmen
t
Tria
l tre
atm
ents
MA
L–PD
T
sing
le s
essi
on v
s M
AL–
PDT
2
sess
ions
(1
wk
apar
t)In
terv
enti
on M
AL–
PDT
sin
gle
sess
ion:
Any
lesi
on c
rust
was
re
mov
ed u
sing
a c
uret
te o
r sc
alpe
l (w
ithou
t an
aest
hetic
) an
d a
1-m
m-t
hick
laye
r of
MA
L (M
etvi
x,
160
mg/
g) w
as a
pplie
d to
eac
h le
sion
and
5 m
m o
f sur
roun
ding
tis
sue
and
cove
red
with
an
occl
usiv
e dr
essi
ng fo
r m
ean
of
3 hr
. The
dre
ssin
g w
as r
emov
ed
and
the
crea
m w
ashe
d of
f with
0.
9% s
alin
e so
lutio
n im
med
iate
ly
befo
re il
lum
inat
ion,
for
mea
n of
8
min
, with
red
LED
ligh
t (p
eak
wav
elen
gth
634
± 3
nm, l
ight
dos
e 37
J/cm
2 , ir
radi
ance
50
mW
/cm
2 at
50 m
m fr
om s
kin)
. Re-
trea
tmen
t if
ther
e w
as a
non
-CR
afte
r 3
mth
Com
para
tor
MA
L–PD
T t
wo
sess
ions
: See
abo
ve, b
ut t
wo
trea
tmen
t se
ssio
ns, 1
wk
apar
t
Mor
bidi
ty A
naly
ses
base
d on
400
lesi
ons
(198
sin
gle
sess
ion;
202
dou
ble
sess
ion
MA
L–PD
T). T
he le
sion
C
R r
ates
wer
e si
mila
r (8
1% s
ingl
e tr
eatm
ent
vs 8
7%
2 tr
eatm
ents
). A
furt
her
22 le
sion
s sh
owed
a C
R
afte
r re
-tre
atm
ent
(incr
easi
ng t
he C
R fo
r th
e si
ngle
tr
eatm
ent
grou
p to
92%
). Si
ngle
and
tw
o-tr
eatm
ent
sche
dule
s ha
d si
mila
r C
Rs
for
thin
lesi
ons
(93%
vs
89%
), bu
t no
t fo
r m
oder
atel
y th
ick
lesi
ons
(70%
vs
84%
), al
thou
gh a
gain
thi
s im
prov
ed a
fter
re-t
reat
men
t (8
8%)
QoL
and
ret
urn
to n
orm
al a
ctiv
ity
Cos
met
ic
outc
ome
was
rat
ed a
s ex
celle
nt fo
r ea
ch o
f fou
r pa
ram
eter
s in
> 7
5% o
f les
ions
in e
ach
grou
p. 66
%
of s
ingl
e tr
eatm
ent
patie
nts,
who
had
pre
viou
sly
been
tre
ated
with
cry
othe
rapy
, pre
ferr
ed P
DT
to
cryo
ther
apy
vs 5
8% in
the
tw
o-tr
eatm
ent
grou
pA
Es A
Es w
ere
repo
rted
in 4
2 si
ngle
-tre
atm
ent
patie
nts
and
in 5
3 tw
o-tr
eatm
ent
patie
nts.
Mos
t lo
cal A
Es w
ere
of m
ild t
o m
oder
ate
inte
nsity
and
of
rela
tivel
y sh
ort
dura
tion.
Bur
ning
of s
kin
occu
rred
in
15%
of s
ingl
e tr
eatm
ent
patie
nts
vs 1
9% o
f the
tr
eatm
ent
grou
p, w
here
as p
ain
occu
rred
in 9
% a
nd
18%
of p
atie
nts,
resp
ectiv
ely.
One
pat
ient
ran
dom
ised
to
tw
o se
ssio
ns d
isco
ntin
ued
due
to m
oder
ate
eryt
hem
a (w
hich
res
olve
d co
mpl
etel
y)
Aut
hors
’ con
clus
ions
Si
ngle
MA
L–PD
T t
reat
men
t is
as
effe
ctiv
e as
a t
wo-
trea
tmen
t sc
hedu
le fo
r th
in A
K le
sion
s. R
epea
ted
trea
tmen
t is
rec
omm
ende
d fo
r th
icke
r or
non
-re
spon
ding
lesi
ons
Bri
ef s
tudy
app
rais
al
Alth
ough
thi
s st
udy
appe
ars
to h
ave
been
qui
te w
ell
cond
ucte
d, it
was
unc
lear
w
heth
er t
he o
utco
me
asse
ssor
s w
ere
blin
ded
to t
reat
men
t al
loca
tion.
21
cen
tres
rec
ruite
d th
e 21
1 pa
tient
s (a
roun
d fiv
e pa
rtic
ipan
ts p
er c
entr
e on
ave
rage
) in
crea
sing
the
po
ssib
ility
tha
t pr
otoc
ol
devi
atio
n an
d in
stitu
tiona
l di
ffere
nces
wou
ld a
ffect
re
sults
. p-v
alue
s w
ere
not
repo
rted
Appendix 13
212
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
213Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Tou
ma
et a
l. (2
003)
39
Dat
a so
urce
Abs
trac
tC
ount
ry U
SALa
ngua
ge E
nglis
hSt
udy
desi
gn R
CT
No.
of p
arti
cipa
nts
Tota
l: 18
Inte
rven
tion:
Not
sta
ted
Com
para
tor:
Not
sta
ted
2nd
Com
para
tor:
Not
st
ated
No.
of r
ecru
itin
g ce
ntre
s N
ot s
tate
dFo
llow
-up
peri
od a
nd
freq
uenc
y D
ay 1
, the
n at
1
wk,
and
1 an
d 5
mth
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
lesi
on
and
hist
olog
y N
on-
hype
rtro
phic
AK
Mai
n el
igib
ility
cr
iter
ia P
atie
nts
with
at
leas
t fo
ur n
on-
hype
rtro
phic
AK
and
di
ffuse
pho
toda
mag
ePa
tien
t ch
arac
teri
stic
s N
ot
stat
edC
onco
mit
ant
trea
tmen
t N
ot s
tate
d
Tria
l tre
atm
ents
ALA
–PD
T, 1-
hr
incu
batio
n vs
2-h
r in
cuba
tion
vs 3
-hr
incu
batio
nIn
terv
enti
on 1
-hr
incu
batio
n: P
re-
trea
tmen
t w
ith 4
0% u
rea
crea
m
(pen
etra
tion
enha
ncer
) an
d xy
loca
ine
HC
L 3%
(pa
in c
ontr
ol)
follo
wed
by
20%
ALA
–PD
T w
ith 4
17-n
m b
lue
light
. Fu
rthe
r PD
T p
aram
eter
s w
ere
not
repo
rted
Com
para
tor
2 hr
incu
batio
n: S
ee a
bove
2nd
com
para
tor
3-hr
incu
batio
n: S
ee
abov
e
Mor
bidi
ty R
esul
ts n
ot b
roke
n do
wn
by t
reat
men
t gr
oup,
but
it w
as r
epor
ted
that
the
re w
as n
o ef
fect
of A
LA
incu
batio
n tim
e or
ure
a cr
eam
on
any
of t
he m
easu
red
outc
omes
. At
1 m
th,
90%
of A
Ks
had
clea
red
(ana
lysi
s on
17
patie
nts)
QoL
and
ret
urn
to n
orm
al a
ctiv
ity
Patie
nt s
atis
fact
ion
with
cos
met
ic r
esul
ts
was
rep
orte
d as
mod
erat
ely
high
, and
all
patie
nts
com
men
ted
on im
prov
ed s
kin
text
ure
AE
s Ph
otot
oxic
rea
ctio
ns w
ere
wel
l to
lera
ted
Aut
hors
’ con
clus
ions
Sho
rt
incu
batio
n (1
–3 h
r) b
road
are
a A
LA–P
DT
ap
pear
s as
effe
ctiv
e in
era
dica
ting
AK
s as
the
long
incu
batio
n ap
plic
atio
n, w
ith
tole
rabl
e ph
otot
oxic
ityB
rief
stu
dy a
ppra
isal
Litt
le
info
rmat
ion
on m
etho
ds a
nd v
ery
limite
d re
sults
pre
sent
ed fo
r th
is v
ery
smal
l stu
dy. T
he c
oncl
usio
ns a
ppea
r in
appr
opri
ate
if th
ey w
ere
base
d on
the
st
udy
resu
lts, a
s sh
ort
incu
batio
n ap
pear
s to
be
defin
ed a
s 1–
3 hr
, yet
no
grou
p re
ceiv
ed lo
ng in
cuba
tion
trea
tmen
t
Appendix 13
212
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
213Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
W
ennb
erg
et a
l. (2
008)
59
Link
ed
publ
icat
ions
176–
178
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry N
ot
stat
ed, ‘E
urop
e’La
ngua
ge E
nglis
hSt
udy
desi
gn R
CT
No.
of
part
icip
ants
Tota
l: 81
(88
9 le
sion
s, 90
% A
K)
Inte
rven
tion:
476
le
sion
sC
ompa
rato
r: 41
3 le
sion
sN
o. o
f rec
ruit
ing
cent
res
11Fo
llow
-up
peri
od
and
freq
uenc
y 3,
9, 1
5, 2
1 an
d 27
mth
afte
r in
itial
tr
eatm
ent
Trea
tmen
t in
tent
ion
Cur
ativ
e.
Thi
s tr
ial a
imed
to
trea
t ex
istin
g le
sion
s an
d al
so p
reve
nt r
ecur
renc
e.
Onl
y re
spon
se r
ates
and
cos
met
ic
outc
omes
hav
e be
en r
epor
ted
here
Type
(s)
of le
sion
and
his
tolo
gy
AK
(so
me
BCC
and
SC
C in
situ
in
clud
ed b
ut d
ata
not
repo
rted
)M
ain
elig
ibili
ty c
rite
ria
Org
an
tran
spla
nt r
ecip
ient
s w
ho h
ad
rece
ived
imm
unos
uppr
essi
ve
ther
apy
for
mor
e th
an 3
yr a
nd h
ad
betw
een
two
and
10 le
sion
s in
tw
o sy
mm
etri
cal 5
0-cm
2 con
tral
ater
al
area
s on
the
face
, sca
lp, n
eck,
trun
k or
ex
trem
ities
. All
patie
nts
wer
e re
quire
d to
hav
e re
ceiv
ed a
t le
ast
one
prev
ious
tr
eatm
ent
for
the
lesi
ons.
Excl
usio
n cr
iteri
a w
ere
repo
rted
Pati
ent
char
acte
rist
ics
% M
ale:
68A
ge r
ange
: 30–
78 yr
Med
ian
age:
57 yr
Mos
t pa
tient
s ha
d Fi
tzpa
tric
k sk
in
type
s I–
III, o
rgan
tra
nspl
anta
tion
occu
rred
bet
wee
n 3
and
34 yr
pr
evio
usly
(m
edia
n 16
yr)
with
the
m
ajor
ity m
ore
than
10
yr p
rior
to
trea
tmen
t. Se
lect
ed t
reat
men
t ar
eas
wer
e m
ostly
on
the
face
, sca
lp o
r ex
trem
ities
. AK
s w
ere
mos
tly g
rade
I or
II a
nd a
lmos
t al
l wer
e ≤
10 m
m in
di
amet
erC
onco
mit
ant
trea
tmen
t N
ot
stat
ed
Tria
l tre
atm
ents
MA
L–PD
T v
s in
vest
igat
or’s
choi
ce o
f tre
atm
ent
(with
in-p
artic
ipan
t co
mpa
riso
n)In
terv
enti
on M
AL–
PDT:
2
trea
tmen
ts w
ere
give
n, 1
wk
apar
t (b
asel
ine
and
1 w
k af
ter
rand
omis
atio
n). A
dditi
onal
sin
gle
trea
tmen
ts w
ere
give
n at
3, 9
and
15
mth
for
a to
tal o
f five
tre
atm
ents
. A
ny v
isib
le le
sion
s at
21
and
27 m
th
wer
e tr
eate
d at
the
inve
stig
ator
s’
disc
retio
n. L
esio
ns w
ere
prep
ared
us
ing
a sm
all c
uret
te t
o de
brid
e th
e ar
ea. M
AL
160
mg/
g cr
eam
app
lied
in
1-m
m la
yer
to 5
0-cm
2 tre
atm
ent
area
an
d co
vere
d fo
r 3
hr w
ith a
n oc
clus
ive
dres
sing
. Exc
ess
crea
m w
as r
emov
ed
with
sal
ine
and
the
area
illu
min
ated
w
ith n
on-c
oher
ent
red
light
from
a
lam
p (6
30 n
m, l
ight
dos
e 37
J/cm
2 ).
Patie
nts’
eye
s w
ere
prot
ecte
d du
ring
tr
eatm
ent.
Fans
and
col
d w
ater
sp
rayi
ng w
ere
used
for
all p
atie
nts
to
min
imis
e pa
inC
ompa
rato
r C
ontr
ol a
rea
was
tr
eate
d at
the
inve
stig
ator
’s di
scre
tion
utili
sing
any
sui
tabl
e th
erap
y in
ac
cord
ance
with
nor
mal
clin
ical
pr
actic
e EX
CEP
T 5
-FU
cre
am o
r im
iqui
mod
cre
am. T
reat
men
t w
as
carr
ied
out
at b
asel
ine
and
3, 9
and
15
mth
late
r. Any
vis
ible
lesi
ons
at 2
1 or
27
mth
wer
e tr
eate
d ac
cord
ing
to
the
inve
stig
ator
’s pr
efer
ence
. Con
trol
tr
eatm
ents
util
ised
: cry
othe
rapy
(83
%)
cure
ttag
e an
d ca
uter
y (4
%)
lase
r th
erap
y (2
%)
surg
ery
(1%
)
Mor
bidi
ty T
his
tria
l aim
ed t
o tr
eat
exis
ting
lesi
ons
and
also
pre
vent
re
curr
ence
. Onl
y re
spon
se r
ates
an
d co
smet
ic o
utco
mes
hav
e be
en
repo
rted
her
e. L
esio
n C
R r
ate
at
3 m
th: M
AL–
PDT
77%
and
con
trol
74
% (
no p
-val
ue r
epor
ted)
. Les
ion
resp
onse
rat
e at
15
mth
: MA
L–PD
T
88%
and
con
trol
89%
Rec
urre
nce
rate
s fo
r le
sion
s th
at
wer
e pr
esen
t at
bas
elin
e an
d ra
ted
as C
R b
y 3
mth
wer
e si
mila
r in
bot
h gr
oups
(PD
T 2
4% a
nd 2
0% c
ontr
ol)
with
no
sign
ifica
nt d
iffer
ence
QoL
and
ret
urn
to n
orm
al
acti
vity
Cos
met
ic o
utco
mes
wer
e ra
ted
by t
he in
vest
igat
or o
n a
3-po
int
scal
e. O
vera
ll M
AL–
PDT
res
ulte
d in
mor
e fa
vour
able
out
com
es
than
the
con
trol
tre
atm
ents
for
hypo
pigm
enta
tion
(p <
0.0
01).
At
15 m
th, m
ore
hypo
pigm
enta
tion
was
rep
orte
d in
the
con
trol
gro
up
and
obvi
ous
hypo
pigm
enta
tion
was
0%
(M
AL–
PDT
) vs
25%
(co
ntro
l).
No
sign
ifica
nt d
iffer
ence
was
foun
d be
twee
n gr
oups
for
scar
form
atio
nA
Es
Loca
l AEs
ass
ocia
ted
with
M
AL–
PDT
wer
e re
port
ed b
y 75
% o
f pa
tient
s al
thou
gh m
ost
wer
e tr
ansi
ent
and
reso
lved
with
in 1
wk
(ery
them
a, pa
in a
nd c
rust
ing)
. 6%
of p
atie
nts
disc
ontin
ued
MA
L–PD
T d
ue t
o pa
in;
pain
was
judg
ed a
s se
vere
in 1
7 ou
t of
420
tre
atm
ent
sess
ions
but
mos
t re
port
ed w
ere
of m
oder
ate
pain
. 48
% o
f pat
ient
s re
port
ed A
Es in
the
co
ntro
l are
a in
clud
ing
pain
, ery
them
a, cr
ustin
g or
blis
teri
ng o
f mild
to
mod
erat
e in
tens
ity
Aut
hors
’ con
clus
ions
Tre
atin
g fie
ld c
ance
risa
tion
in o
rgan
tra
nspl
ant
reci
pien
ts w
ith t
opic
al M
AL–
PDT
is
effi
caci
ous
and
gene
rally
wel
l to
lera
ted
(furt
her
conc
lusi
ons
rela
ting
to p
reve
ntio
n of
AK
rep
orte
d)B
rief
stu
dy a
ppra
isal
Thi
s st
udy
was
pri
mar
ily in
tend
ed
to e
valu
ate
prop
hyla
ctic
PD
T in
im
mun
osup
pres
sed
patie
nts
and
this
sh
ould
be
born
e in
min
d. F
ew d
etai
ls
wer
e pr
ovid
ed a
bout
con
ceal
men
t of
allo
catio
n, a
nd b
lindi
ng w
as n
ot
used
. The
con
trol
tre
atm
ent
was
not
pr
edefi
ned
and
inte
rcen
tre
diffe
renc
es
are
likel
y to
hav
e im
pact
ed o
n th
e re
sults
(of
whi
ch fe
w fi
gure
s w
ere
prov
ided
). A
s a
com
para
tive
stud
y, th
e re
sults
sho
uld
be c
onsi
dere
d w
ith
caut
ion
and
may
not
be
relia
ble
Appendix 13
214 Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Wie
gell
et
al. (
2008
)53
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry D
enm
ark
Lang
uage
Eng
lish
Stud
y de
sign
RC
TN
o. o
f pa
rtic
ipan
tsTo
tal:
30 (
29
trea
ted)
Inte
rven
tion:
30
(29
trea
ted)
C
ompa
rato
r: 30
(29
tr
eate
d)N
o. o
f rec
ruit
ing
cent
res
One
Follo
w-u
p pe
riod
an
d fr
eque
ncy
FU
at 1
–3 d
(A
Es)
and
3 m
th (
CR
)
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
lesi
on a
nd
hist
olog
y A
KM
ain
elig
ibili
ty c
rite
ria
Patie
nts
with
AK
s sy
mm
etri
cally
di
stri
bute
d on
the
face
or
scal
p. Pr
egna
nt o
r la
ctat
ing
wom
en
wer
e ex
clud
edPa
tien
t ch
arac
teri
stic
s%
Mal
e: 79
Age
ran
ge: 6
3–90
yrM
ean
age:
78 yr
Mos
t le
sion
s w
ere
grad
e I,
with
ar
ound
a t
hird
gra
de II
and
ver
y sm
all n
umbe
r w
ere
grad
e III
Con
com
itan
t tr
eatm
ent
Suns
cree
n fo
r ex
pose
d ar
eas
not
cove
red
by t
reat
men
t
Tria
l tre
atm
ents
MA
L–PD
T w
ith
dayl
ight
vs
MA
L–PD
T w
ith r
ed L
ED
(with
in-p
artic
ipan
t co
mpa
riso
n)In
terv
enti
on P
DT
with
day
light
: Bef
ore
trea
tmen
t, le
sion
s w
ere
coun
ted,
gra
ded,
m
appe
d, a
nd p
hoto
grap
hed.
AK
lesi
ons
of fa
ce o
r sc
alp
wer
e m
arke
d in
to t
wo
sym
met
rica
l tre
atm
ent
area
s (~
80 cm
2
each
) an
d sc
ales
and
hyp
erke
rato
ses
wer
e re
mov
ed u
sing
a c
uret
te. A
roun
d 1
g of
MA
L cr
eam
was
app
lied
to e
ach
area
and
cov
ered
with
a d
ress
ing
and
light
-impe
rmea
ble
lead
rub
ber.
Follo
win
g 30
min
indo
ors,
the
dayl
ight
are
a ha
d th
e dr
essi
ng r
emov
ed a
nd p
atie
nts
spen
t 2.
5 hr
out
side
in d
aylig
ht (
mea
n ef
fect
ive
tota
l dos
e 43
J/cm
2 , m
ean
effe
ctiv
e re
d lig
ht d
ose
1.9
J/cm
2 , pa
tient
s tr
eate
d in
pe
riod
bet
wee
n Ju
ly a
nd S
epte
mbe
r),
befo
re r
etur
ning
to
have
MA
L cr
eam
from
bo
th t
reat
men
t ar
eas
rem
oved
. The
are
a ra
ndom
ised
to
red
LED
ligh
t w
as t
reat
ed
with
a li
ght
dose
of 3
7 J/c
m2 (
effe
ctiv
e re
d lig
ht d
ose
1.2
J/cm
2 , pe
ak ir
radi
ance
at
632
nm
) af
ter
cove
ring
the
day
light
tr
eatm
ent
area
with
ligh
t-im
perm
eabl
e ru
bber
Com
para
tor
PDT
with
red
LED
: See
ab
ove
Mor
bidi
ty A
t 3
mth
the
abs
olut
e de
crea
se in
the
m
ean
num
ber
of le
sion
s co
mpa
red
to b
asel
ine
was
8.0
(71
%)
in t
he L
ED a
reas
vs
8.4
(79%
) in
the
da
ylig
ht a
reas
(p
= 0.
13 fo
r pe
rcen
tage
, p =
0.5
0 fo
r m
ean
num
ber)
QoL
and
ret
urn
to n
orm
al a
ctiv
ity
Eigh
teen
pa
tient
s (6
2%)
pref
erre
d th
e da
ylig
ht t
reat
men
t, fo
ur (
14%
) LE
D t
reat
men
t, an
d si
x (2
1%)
had
no
pref
eren
ceA
Es A
naly
ses
base
d on
24
patie
nts:
The
day
light
are
as
wer
e si
gnifi
cant
ly le
ss p
ainf
ul o
n a
10-p
oint
VA
S sc
ale
than
the
LED
are
as (
mea
n m
axim
al p
ain
scor
e, 2
.0
for
dayl
ight
vs
6.7
for
LED
, p <
0.0
001)
. In
the
LED
lig
ht g
roup
, 15
patie
nts
need
ed c
old
wat
er s
pray
to
mak
e pa
in t
oler
able
, and
one
-hal
f of t
hese
pat
ient
s ne
eded
one
or
two
brea
ks d
urin
g ill
umin
atio
n. In
tw
o pa
tient
s th
is w
as n
ot e
noug
h, s
o tr
eatm
ents
wer
e st
oppe
d af
ter
one-
third
of i
llum
inat
ion
time.
Pai
n sc
ores
6 h
r af
ter
LED
tre
atm
ent
wer
e no
t si
gnifi
cant
ly
diffe
rent
(m
ean
max
imal
sco
re o
f 1 fo
r da
ylig
ht v
s 1.
3 fo
r LE
D, p
= 0
.14)
. Bot
h ar
eas
deve
lope
d er
ythe
ma
and
crus
ting
afte
r tr
eatm
ent.
The
se A
Es w
ere
mos
t se
vere
in t
he d
aylig
ht a
rea
in 1
0 pa
tient
s (4
2%),
in
the
LED
are
a in
five
pat
ient
s (2
1%)
and
ther
e w
as n
o di
ffere
nce
betw
een
the
area
s in
nin
e pa
tient
s (3
8%)
Aut
hors
’ co
nclu
sion
s C
ontin
uous
act
ivat
ion
PDT
usi
ng d
aylig
ht
expo
sure
was
as
effe
ctiv
e as
, and
be
tter
tol
erat
ed t
han,
co
nven
tiona
l PD
TB
rief
stu
dy
appr
aisa
l Thi
s w
as
a ge
nera
lly w
ell
cond
ucte
d bu
t sm
all
stud
y an
d th
e re
sults
ap
pear
like
ly t
o be
re
liabl
e. It
sho
uld
be n
oted
tho
ugh
that
six
pat
ient
s ha
d pr
evio
usly
rec
eive
d PD
T in
the
tre
ated
ar
eas
(alth
ough
mor
e th
an 1
yr b
efor
e th
e st
udy)
, and
tha
t th
e LE
D il
lum
inat
ion
time
was
not
cle
arly
sta
ted
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
215
Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Wie
gell
et a
l. (20
08)40
Dat
a so
urce
Abs
trac
tC
ount
ry D
enm
ark
Lang
uage
Eng
lish
Stud
y de
sign
RC
TN
o. o
f par
tici
pant
sTo
tal:
29In
terv
entio
n: 2
9C
ompa
rato
r: 29
No.
of r
ecru
itin
g ce
ntre
s N
ot
stat
edFo
llow
-up
peri
od a
nd
freq
uenc
y FU
at
3 m
th
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
lesi
on a
nd h
isto
logy
A
KM
ain
elig
ibili
ty c
rite
ria
Patie
nts
with
AK
of t
he fa
ce a
nd s
calp
Pati
ent
char
acte
rist
ics
Not
sta
ted
Con
com
itan
t tr
eatm
ent
Not
st
ated
Tria
l tre
atm
ents
PD
T w
ith
8% M
AL
vs P
DT
with
16%
MA
L (w
ithin
-par
ticip
ant
com
pari
son)
Inte
rven
tion
PD
T 8
% M
AL:
Pa
tient
s w
ere
give
n bo
th
trea
tmen
ts, r
ando
mis
ed t
o tw
o sy
mm
etri
c ar
eas,
one
area
was
gi
ven
8% M
AL
crea
m a
nd t
he
othe
r 16
% M
AL
crea
m. P
atie
nts
wer
e se
nt h
ome
and
inst
ruct
ed
to s
pend
as
muc
h tim
e as
po
ssib
le o
utsi
de, i
n da
ylig
ht.
Patie
nts
spen
t an
ave
rage
of
210
min
out
door
s (r
ange
62
–372
min
). Li
ght
expo
sure
was
m
easu
red
usin
g an
ele
ctro
nic
dosi
met
er w
atch
Com
para
tor
PDT
16%
MA
L:
See
abov
e
Mor
bidi
ty A
t 3
mth
, the
re w
as
no s
igni
fican
t di
ffere
nce
in C
R
rate
(77
% in
16%
are
a vs
80%
in
8% a
rea)
, p =
0.3
7Q
oL a
nd r
etur
n to
nor
mal
ac
tivi
ty N
ot a
sses
sed
AE
s Er
ythe
ma
and
crus
ting
occu
rred
in b
oth
trea
tmen
ts (a
nd
wer
e si
mila
r to
infla
mm
atio
n se
en a
fter
conv
entio
nal P
DT
). Pa
in d
iari
es w
ere
used
but
not
re
port
ed b
y in
terv
entio
n ar
m
Aut
hors
’ con
clus
ions
PD
T
usin
g da
ylig
ht a
ctiv
atio
n w
ill
mak
e A
K t
reat
men
t m
ore
time
and
cost
-effe
ctiv
e, a
nd m
ore
conv
enie
nt fo
r th
e pa
tient
Bri
ef s
tudy
app
rais
al T
he
auth
ors
com
pare
d ov
eral
l pai
n sc
ores
, and
AEs
in a
sm
all s
ampl
e,
with
tho
se s
een
in c
onve
ntio
nal
PDT,
but
usin
g a
com
para
tor
trea
tmen
t of
con
vent
iona
l PD
T
in t
his
stud
y w
ould
hav
e be
en
muc
h m
ore
info
rmat
ive.
Thi
s ab
stra
ct a
lso
feat
ured
min
imal
re
port
ing
of m
etho
ds a
nd r
esul
ts
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
217
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
217
Appendix 14 Bowen’s disease data extraction
Appendix 14
218
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
219Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
de
Haa
s et
al
. (20
07)69
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry T
he
Net
herl
ands
Lang
uage
Eng
lish
Stud
y de
sign
RC
TN
o. o
f par
tici
pant
sTo
tal:
40 (
50 B
owen
’s di
seas
e pa
tche
s)In
terv
entio
n: 2
5 le
sion
s (p
artic
ipan
t no
. no
t st
ated
)C
ompa
rato
r: 25
le
sion
s (p
artic
ipan
t no
. no
t st
ated
)N
o. o
f rec
ruit
ing
cent
res
One
Follo
w-u
p pe
riod
an
d fr
eque
ncy
4 w
k, th
en a
t 3
mth
inte
rval
s up
to
28 m
th
Type
(s)
of le
sion
an
d hi
stol
ogy
Bow
en’s
dise
ase
Mai
n el
igib
ility
cr
iter
ia N
ot s
tate
dPa
tien
t ch
arac
teri
stic
s%
Mal
e: 43
Age
ran
ge: 4
9–91
yr
Mea
n ag
e: 74
yrM
ean
lesi
on d
iam
eter
: 14
.5 m
m (
rang
e 5–
40 m
m)
Loca
tions
: Tru
nk 1
2,
low
er le
g 11
, han
d 8,
ear
7, u
pper
leg
4,
chee
k an
d/or
nos
e 3,
ey
elid
2, a
rm 1
, fro
ntal
an
d/or
tem
pora
l are
a 1,
sca
lp 1
The
sam
ple
incl
uded
se
ven
orga
n re
cipi
ents
Con
com
itan
t tr
eatm
ent
Lido
cain
e,
2% w
ithou
t ad
rena
line
was
use
d if
patie
nts
requ
ired
it
Tria
l tre
atm
ents
ALA
–PD
T u
sing
a
sing
le il
lum
inat
ion
vs A
LA–P
DT
with
a
twof
old
illum
inat
ion
Inte
rven
tion
Sin
gle
Illum
inat
ion:
Sur
face
sc
ale
or c
rust
s w
ere
rem
oved
. 20%
ALA
, lo
cally
pro
duce
d, w
as a
pplie
d to
pica
lly a
nd
left
in p
lace
for
4 hr
with
a m
argi
n of
1 cm
. A
dio
de la
ser
and
light
em
ittin
g di
ode
prov
ided
illu
min
atio
n at
a w
avel
engt
h of
63
0 nm
, 4 h
r af
ter A
LA a
pplic
atio
n at
a
dose
of 7
5 J/c
m2
Furt
her
PDT
par
amet
ers
wer
e no
t re
port
edC
ompa
rato
r Tw
ofol
d ill
umin
atio
n: A
s fo
r si
ngle
illu
min
atio
n ex
cept
pat
ches
w
ere
light
tre
ated
4 a
nd 6
hr
afte
r ALA
ap
plic
atio
n at
dos
es o
f 20
and
80 J/
cm2 ,
resp
ectiv
ely,
sepa
rate
d by
a 2
-hr
dark
in
terv
al. E
ach
illum
inat
ion
was
del
iver
ed a
t 50
mW
/cm
2
Mor
bidi
ty In
the
sin
gle
illum
inat
ion
grou
p, C
R w
as s
een
in 2
2 pa
tche
s (8
0%)
at 1
2 m
th. I
n th
e tw
ofol
d-ill
umin
atio
n gr
oup
CR
was
see
n in
22
patc
hes
(88%
) (N
S). P
atie
nts
repo
rted
a 3
-wk
max
imum
he
alin
g tim
e, w
hich
was
not
diff
eren
t be
twee
n tr
eatm
ents
QoL
and
ret
urn
to n
orm
al a
ctiv
ity
Not
ass
esse
dA
Es A
ll pa
tient
s in
bot
h gr
oups
ex
peri
ence
d so
me
disc
omfo
rt d
urin
g tr
eatm
ent
but
all fi
nish
ed t
hera
py. N
o SA
Es w
ere
seen
in e
ither
gro
up. I
n th
e si
ngle
-illu
min
atio
n gr
oup
none
of t
he
patie
nts
com
plai
ned
of p
ain
duri
ng
trea
tmen
t. In
the
tw
ofol
d-ill
umin
atio
n gr
oup
five
patie
nts
com
plai
ned
abou
t pa
in
in t
he t
reat
men
t of
six
pat
ches
. Lid
ocai
ne
with
out
adre
nalin
e w
as u
sed
in fo
ur
patc
hes
Aut
hors
’ con
clus
ions
ALA
–PD
T
may
offe
r th
e be
st t
reat
men
t op
tion
for
Bow
en’s
dise
ase.
Thi
s st
udy
show
s th
e po
tent
ial o
f lig
ht fr
actio
natio
n fo
r en
hanc
ing
the
resp
onse
of t
he d
isea
se t
o A
LA–P
DT
and
illu
stra
tes
the
need
for
a la
rger
, sui
tabl
y po
wer
ed t
rial
to
dete
rmin
e if
the
effe
ct is
sta
tistic
ally
sig
nific
ant
Bri
ef s
tudy
app
rais
al T
his
was
a
smal
l tri
al w
ith u
ncle
ar m
etho
ds o
f ra
ndom
isat
ion
and
blin
ding
. Tre
atm
ent
met
hods
wer
e re
port
ed b
ut n
ot a
ll ou
tcom
es w
ere
deta
iled.
Thi
s st
udy
show
s th
e po
tent
ial o
f PD
T a
nd it
s en
hanc
emen
t th
roug
h lig
ht fr
actio
natio
n bu
t w
ould
nee
d co
nfirm
atio
n, a
s th
e au
thor
s st
ate,
in a
n ad
equa
tely
pow
ered
tri
al
Appendix 14
218
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
219
Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Lui
et a
l. (20
04)68
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ries
Can
ada,
USA
Lang
uage
Eng
lish
Stud
y de
sign
RC
TN
o. o
f par
tici
pant
sTo
tal:
Not
sta
ted
by
diag
nosi
s (3
4 le
sion
s)In
terv
entio
n: N
ot s
tate
d by
dia
gnos
is (
27 le
sion
s)C
ompa
rato
r: N
ot s
tate
d by
dia
gnos
is (
one
lesi
on)
2nd
Com
para
tor:
Not
st
ated
by
diag
nosi
s (s
ix
lesi
ons)
No.
of r
ecru
itin
g ce
ntre
s Fo
urFo
llow
-up
peri
od a
nd
freq
uenc
y 6
wk,
and
3, 6
, 12
, 18
and
24 m
th
Type
(s)
of le
sion
and
hi
stol
ogy
Supe
rfici
al
BCC
, 277
lesi
ons
(66%
); nB
CC
, 93
lesi
ons
(22%
); Bo
wen
’s di
seas
e,
34 le
sion
s (8
%);
BCC
un
spec
ified
17
lesi
ons
(4%
)M
ain
elig
ibili
ty
crit
eria
Pat
ient
s w
ith
at le
ast
two
biop
sy-
prov
en s
uper
ficia
l or
nBC
C o
r Bo
wen
’s le
sion
sPa
tien
t ch
arac
teri
stic
s N
ot
stat
ed fo
r Bo
wen
’s gr
oup
Con
com
itan
t tr
eatm
ent
Ora
l an
alge
sics
for
pain
Tria
l tre
atm
ents
PD
T a
t 60
J/cm
2 vs
PDT
at
120
J/cm
2 vs
PDT
at
180
J/cm
2
Inte
rven
tion
PD
T a
t 60
J/cm
2 : 10
min
intr
aven
ous
infu
sion
of
14 m
g/m
2 ver
tepo
rfin
follo
wed
1–3
hr
late
r by
exp
osur
e to
60
J/cm
2 of
red
light
(68
8 ±
10 n
m)
from
a n
on-
ther
mal
LED
pan
el. T
he e
xpos
ed a
rea
had
a m
argi
n of
3–4
mm
aro
und
the
lesi
on. T
he ir
radi
ance
del
iver
ed w
as
200
± 40
mW
/cm
2 . Tum
ours
re-
trea
ted
at
3 m
th if
nec
essa
ry (
with
dos
e in
crea
sed
to 1
8 m
g/m
2 )C
ompa
rato
r PD
T a
t 12
0 J/c
m2 :
See
abov
e2n
d co
mpa
rato
r PD
T a
t 18
0 J/c
m2 :
See
abov
e
Mor
bidi
ty A
t 6
mth
, the
hi
stop
atho
logi
cal r
espo
nse
(i.e.
no
resi
dual
tum
our)
was
85%
at
60 J/
cm2 ,
100%
at
120
J/cm
2 , an
d 50
% a
t 18
0 J/c
m2
QoL
and
ret
urn
to n
orm
al a
ctiv
ity
Ass
esse
d bu
t no
t re
port
ed fo
r Bo
wen
’s gr
oup
AE
s Ass
esse
d bu
t no
t re
port
ed fo
r Bo
wen
’s gr
oup
Aut
hors
’ con
clus
ions
A s
ingl
e co
urse
of
ver
tepo
rfin
PDT
sho
wed
tre
atm
ent
bene
fit fo
r pa
tient
s w
ith m
ultip
le n
on-
mel
anom
a sk
in c
ance
rsB
rief
stu
dy a
ppra
isal
The
re w
as a
la
ck o
f inf
orm
atio
n on
issu
es s
uch
as
blin
ding
and
allo
catio
n co
ncea
lmen
t, an
d th
e au
thor
s di
d no
t pr
esen
t m
any
resu
lts a
nd p
opul
atio
n de
tails
by
diag
nosi
s. It
is t
here
fore
diffi
cult
to
mak
e an
y re
liabl
e co
nclu
sion
s ab
out
the
effic
acy
of v
erte
porfi
n in
pat
ient
s w
ith
Bow
en’s
dise
ase,
par
ticul
arly
as
they
fo
rmed
a s
mal
l pro
port
ion
of t
he o
vera
ll nu
mbe
r of
lesi
ons
Appendix 14
220
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
221Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Mor
ton
et a
l. (2
000)
70
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry U
KLa
ngua
ge E
nglis
hSt
udy
desi
gn R
CT
No.
of p
arti
cipa
nts
Tota
l: 19
(70
lesi
ons)
ra
ndom
ised
16
(61
lesi
ons)
follo
wed
up
Inte
rven
tion:
32
lesi
ons
(no
of p
atie
nts
not
spec
ified
)C
ompa
rato
r: 29
lesi
ons
(no
of p
atie
nts
not
spec
ified
)N
o. o
f rec
ruit
ing
cent
res
Not
sta
ted
Follo
w-u
p pe
riod
an
d fr
eque
ncy
Afte
r cl
eara
nce,
all
patie
nts
wer
e re
view
ed a
t m
onth
ly
inte
rval
s, up
to
12 m
th
Type
(s)
of le
sion
and
hi
stol
ogy
Bow
en’s
dise
ase
Mai
n el
igib
ility
cri
teri
a Bi
opsy
-pro
ven
dise
ase
with
indi
vidu
al le
sion
s of
≤2
1 m
m in
dia
met
er. N
o le
sion
had
bee
n pr
evio
usly
tr
eate
dPa
tien
t ch
arac
teri
stic
s A
ge r
ange
: 50–
87 yr
Mea
n ag
e: 73
yrN
o. o
f les
ions
per
pat
ient
va
ried
bet
wee
n on
e an
d si
x (m
edia
n th
ree)
Con
com
itan
t tr
eatm
ent
Loca
l an
aest
hetic
(1%
pla
in
lidoc
aine
by
intr
ader
mal
in
ject
ion)
was
offe
red
duri
ng P
DT
tre
atm
ent
Tria
l tre
atm
ents
ALA
–PD
T w
ith r
ed li
ght
vs A
LA–P
DT
with
gre
en li
ght
Inte
rven
tion
Red
ligh
t: Su
rfac
e cr
usts
wer
e re
mov
ed a
nd t
he s
urfa
ce w
as g
ently
abr
aded
. To
pica
l ALA
in a
n oi
l-in-
wat
er e
mul
sion
was
ap
plie
d to
the
lesi
ons
4 h
pre-
illum
inat
ion.
A
ppro
xim
atel
y 50
mg/
cm2 o
f cre
am
was
app
lied
to c
over
the
ent
ire fi
eld
of
illum
inat
ion,
incl
udin
g a
clin
ical
ly d
isea
se-fr
ee
mar
gin
of a
t le
ast
4 m
m. T
he c
ream
was
kep
t in
pla
ce u
nder
an
occl
usiv
e dr
essi
ngA
‘Pat
erso
n’ la
mp
with
300
W x
enon
sho
rt
arc
plas
ma
disc
harg
e w
as a
djus
ted
usin
g ap
prop
riat
e fil
ters
to
630
± 15
nm
for
red
light
. At
a flu
ence
rat
e of
86
mW
/cm
2 les
ions
re
ceiv
ed 1
25 J/
cm2 o
f red
ligh
tA
rep
eat
trea
tmen
t w
as g
iven
afte
r 2
mth
if
nece
ssar
yC
ompa
rato
r As
for
red
light
exc
ept
a w
avel
engt
h of
540
± 1
5 nm
was
use
d to
de
liver
62.
5 J/c
m2 o
f lig
ht
Mor
bidi
ty In
the
red
ligh
t gr
oup
24 le
sion
s cl
eare
d fo
llow
ing
one
trea
tmen
t an
d a
furt
her
six
afte
r a
repe
at t
reat
men
t gi
ving
an
initi
al
resp
onse
rat
e of
94%
. Eig
htee
n le
sion
s tr
eate
d us
ing
gree
n lig
ht c
lear
ed a
fter
one
trea
tmen
t w
ith a
furt
her
thre
e cl
eari
ng o
n re
peat
giv
ing
an
initi
al r
espo
nse
of 7
2%. D
iffer
ence
in r
espo
nse
was
sta
tistic
ally
sig
nific
ant
(p =
0.0
02).
A h
igh
recu
rren
ce r
ate
was
obs
erve
d in
the
gre
en li
ght
grou
p w
ith s
even
rec
urre
nces
in c
ompa
riso
n w
ith t
wo
lesi
ons
rela
psin
g af
ter
PDT
with
red
lig
ht. O
R fo
r re
curr
ence
= 0
.13
(95%
CI 0
.04
to
0.48
)Q
oL a
nd r
etur
n to
nor
mal
act
ivit
y N
o cl
inic
ally
obv
ious
sca
rs w
ere
evid
ent
at 1
yr in
ei
ther
gro
upA
Es
No
ulce
ratio
n or
infe
ctio
n co
mpl
icat
ing
ther
apy
and
no p
hoto
sens
itivi
ty r
eact
ions
wer
e do
cum
ente
d af
ter
PDT
tre
atm
ent
in e
ither
gr
oup.
No
sign
ifica
nt d
iffer
ence
in p
ain
was
see
n be
twee
n th
e tr
eatm
ent
grou
ps. N
o re
d lig
ht
patie
nts
need
ed a
naes
thes
ia w
here
as t
wo
lesi
ons
(one
pat
ient
) tr
eate
d in
the
gre
en li
ght
grou
p ne
eded
ana
esth
esia
Twel
ve p
atie
nts
rece
ived
bot
h ty
pes
of li
ght.
Four
st
ated
tha
t gr
een
light
was
the
mos
t pa
infu
l, si
x th
at r
ed li
ght
was
the
mos
t pa
infu
l, w
hile
tw
o pa
tient
s co
uld
not
dist
ingu
ish
betw
een
the
light
us
ed
Aut
hors
’ con
clus
ions
G
reen
ligh
t is
less
ef
fect
ive
than
red
ligh
t in
th
e tr
eatm
ent
of B
owen
’s di
seas
e by
ALA
–PD
TB
rief
stu
dy a
ppra
isal
A
sm
all s
tudy
, with
un
clea
r m
etho
ds o
f ra
ndom
isat
ion,
allo
catio
n co
ncea
lmen
t an
d bl
indi
ng
of o
utco
me
asse
ssor
s
Appendix 14
220
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
221Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Mor
ton
et a
l. (1
996)
71
Link
ed p
ublic
atio
ns17
9
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry U
KLa
ngua
ge E
nglis
hSt
udy
desi
gn R
CT
No.
of p
arti
cipa
nts
Tota
l: 19
(40
lesi
ons)
In
terv
entio
n: 2
0 le
sion
s, pa
rtic
ipan
t no
. not
st
ated
Com
para
tor:
20 le
sion
s, pa
rtic
ipan
t no
. not
st
ated
No.
of r
ecru
itin
g ce
ntre
s N
ot s
tate
dFo
llow
-up
peri
od
and
freq
uenc
y 2
d an
d 10
d fo
r AEs
. 2-m
onth
ly
inte
rval
s fo
r cl
inic
al
resp
onse
. Fol
low
ing
clea
ranc
e, 2
-mon
thly
in
terv
als
for
12 m
th fo
r re
curr
ence
and
late
AEs
Mai
n el
igib
ility
cr
iter
ia H
isto
logi
cal
confi
rmat
ion
of
Bow
en’s
with
in
divi
dual
lesi
ons
≤ 21
mm
in d
iam
eter
. N
o le
sion
had
bee
n pr
evio
usly
tre
ated
Pati
ent
char
acte
rist
ics
% M
ale:
16A
ge r
ange
: 62–
88 yr
Mea
n ag
e: 76
yrLo
catio
n an
d no
. of
lesi
ons:
legs
33,
face
fiv
e, h
and
two
Con
com
itan
t tr
eatm
ent
Patie
nts
wer
e of
fere
d lo
cal
anae
sthe
tic (
1%
plai
n lid
ocai
ne b
y in
trad
erm
al in
ject
ion)
du
ring
tre
atm
ent
Tria
l tre
atm
ents
PD
T w
ith A
LA v
s C
ryot
hera
pyIn
terv
enti
on P
DT:
Sur
face
cru
sts
wer
e re
mov
ed a
nd t
he s
urfa
ce g
ently
abr
aded
pri
or
to a
pplic
atio
n w
ith t
opic
al 5
-ALA
in a
n oi
l-in-
wat
er e
mul
sion
20%
. App
roxi
mat
ely
50 m
g/cm
2 of
crea
m w
as a
pplie
d to
cov
er t
he e
ntire
irra
diat
ion
field
incl
udin
g th
e cl
inic
ally
dis
ease
-free
mar
gin.
T
he c
ream
was
kep
t in
pla
ce u
nder
an
occl
usiv
e dr
essi
ngFo
ur h
ours
late
r le
sion
s w
ere
illum
inat
ed w
ith a
pr
otot
ype
lam
p. T
he la
mp
inco
rpor
ated
a 3
00 W
xe
non
shor
t ar
c pl
asm
a di
scha
rge
prod
ucin
g a
cont
inuo
us w
ave
broa
dban
d fla
t sp
ectr
al o
utpu
t ac
ross
the
ent
ire v
isib
le s
pect
rum
. Usi
ng fi
lters
, th
e sp
ectr
al o
utpu
t of
the
lam
p w
as a
djus
ted
to
a 30
-nm
ban
dwid
th, a
bout
630
nm
. To
broa
den
the
trea
tmen
t fie
ld a
nd t
o pr
oduc
e un
iform
ir
radi
atio
n of
the
lesi
ons,
a 25
-mm
col
limat
ing
lens
was
att
ache
d to
the
5-m
m fi
bre
bund
le.
Allo
win
g at
leas
t a
10%
mar
gin
arou
nd le
sion
s in
th
e fie
ld o
f irr
adia
tion
perm
itted
the
tre
atm
ent
of le
sion
s ≤
21 m
m in
dia
met
er, a
t a
fluen
ce r
ate
of 7
0 m
W/c
m2 a
nd a
tre
atm
ent
time
of 3
0 m
in,
lesi
ons
rece
ived
125
J/cm
2 . Fo
llow
ing
ther
apy,
3-m
m p
unch
bio
psie
s w
ere
perf
orm
ed in
lesi
ons
whe
re t
here
was
dou
bt o
ver
clin
ical
cle
aran
ce o
r re
curr
ence
. Rep
eat
trea
tmen
ts w
ere
adm
inis
tere
d if
lesi
ons
pers
iste
dC
ompa
rato
r C
ryot
hera
py: L
iqui
d ni
trog
en
was
app
lied
to le
sion
s vi
a a
hand
-hel
d C
ry-A
c sp
ray.
Afte
r in
itial
ice
field
form
atio
n, t
he fr
eeze
w
as m
aint
aine
d fo
r 20
s. A
sin
gle
free
ze–t
haw
cy
cle
tech
niqu
e w
as u
sed
with
a 2
–3 m
m r
im o
f cl
inic
ally
hea
lthy
tissu
e in
clud
ed in
the
tre
atm
ent
field
. Fol
low
ing
ther
apy,
3-m
m p
unch
bio
psie
s w
ere
perf
orm
ed in
lesi
ons
whe
re t
here
was
do
ubt
over
clin
ical
cle
aran
ce o
r re
curr
ence
. R
epea
t tr
eatm
ents
wer
e ad
min
iste
red
if le
sion
s pe
rsis
ted
Mor
bidi
tyC
lear
ance
afte
r on
e tr
eatm
ent:
PDT,
15 o
f 20
lesi
ons;
cryo
ther
apy,
10 o
f 20
lesi
ons
Cle
aran
ce a
fter
two
trea
tmen
ts: P
DT,
five
rem
aini
ng le
sion
s; cr
yoth
erap
y, si
x le
sion
s T
he r
emai
ning
four
lesi
ons
in t
he c
ryot
hera
py
grou
p re
quire
d a
third
tre
atm
ent.
The
re w
as
no s
igni
fican
t di
ffere
nce
betw
een
the
two
trea
tmen
ts in
cle
aran
ce r
ates
. How
ever
, by
chan
ce le
sion
s tr
eate
d by
PD
T w
ere
over
all
larg
er t
han
thos
e in
the
cry
othe
rapy
gro
up. I
n a
linea
r re
gres
sion
mod
el t
akin
g si
ze o
f les
ion
into
acc
ount
, the
pro
babi
lity
that
a le
sion
of a
ny
size
is c
ompl
etel
y cl
eare
d at
the
1st
tre
atm
ent
was
sig
nific
antly
gre
ater
with
PD
T t
han
with
cr
yoth
erap
y (p
< 0
.01)
. Rec
urre
nce
Rat
e du
ring
12
-mth
follo
win
g cl
inic
al c
lear
ance
: PD
T z
ero;
cr
yoth
erap
y tw
o (6
mth
and
8 m
th).
CR
rat
e w
as, t
here
fore
, 100
% fo
r PD
T a
nd 9
0% fo
r cr
yoth
erap
yQ
oL a
nd r
etur
n to
nor
mal
act
ivit
y V
isib
le
scar
ring
12
mth
follo
win
g cl
eara
nce
(no.
of
lesi
ons)
: PD
T z
ero,
cry
othe
rapy
four
AE
s Pa
in d
urin
g tr
eatm
ent
(no.
of l
esio
ns):
PDT,
six
mild
and
five
mod
erat
e; c
ryot
hera
py, 1
2 m
ild
and
seve
n m
oder
ate
(p =
0.0
1). F
ree
from
pai
n 10
d fo
llow
ing
trea
tmen
t (n
o. o
f les
ions
): PD
T
15; c
ryot
hera
py 1
0A
ll si
x pa
tient
s w
ho r
ecei
ved
both
tre
atm
ents
, du
e to
hav
ing
mul
tiple
lesi
ons,
repo
rted
PD
T a
s le
ss p
ainf
ul. B
liste
ring
(no
. of l
esio
ns):
PDT
zer
o;
cryo
ther
apy
seve
n. U
lcer
atio
n (n
o. o
f les
ions
): PD
T z
ero;
cry
othe
rapy
five
. Sec
onda
ry in
fect
ion
(no.
of l
esio
ns):
PDT
zer
o; c
ryot
hera
py t
wo.
No
phot
osen
sitiv
ity r
eact
ions
occ
urre
d af
ter
PDT
Aut
hors
’ con
clus
ions
PD
T is
at
leas
t as
effe
ctiv
e as
cry
othe
rapy
in t
he
trea
tmen
t of
Bow
en’s
dise
ase
and
was
ass
ocia
ted
in t
his
stud
y w
ith fe
wer
AEs
an
d a
low
er r
ecur
renc
e ra
teB
rief
stu
dy a
ppra
isal
T
his
was
a s
mal
l tri
al u
sing
a
prot
otyp
e la
mp
as a
lig
ht s
ourc
e. R
esul
ts w
ere
repo
rted
by
lesi
on r
athe
r th
an b
y pa
tient
. By
chan
ce
lesi
ons
wer
e si
gnifi
cant
ly
larg
er in
the
PD
T g
roup
but
th
is w
as t
aken
into
acc
ount
w
hen
asse
ssin
g cl
eara
nce
rate
s. T
he r
esul
ts o
f the
tri
al
are
prom
isin
g bu
t w
ould
re
quire
con
firm
atio
n in
la
rger
tri
als
Appendix 14
222
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
223Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Mor
ton
et a
l. (2
006)
73
Link
ed p
ublic
atio
ns18
0–18
4
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ries
Not
sta
ted,
11
Eur
opea
n co
untr
ies
Lang
uage
Eng
lish
Stud
y de
sign
RC
TN
o. o
f par
tici
pant
sTo
tal:
229
rand
omis
ed,
225
trea
ted
(275
le
sion
s)In
terv
entio
n: 9
6 (1
24
lesi
ons)
Com
para
tor:
17 (
24
lesi
ons)
2nd
Com
para
tor:
82 (
91
lesi
ons)
3rd
Com
para
tor:
30 (
36
lesi
ons)
No.
of r
ecru
itin
g ce
ntre
s 40
Follo
w-u
p pe
riod
an
d fr
eque
ncy
3, 1
2 an
d 24
mth
afte
r la
st
trea
tmen
t
Type
(s)
of le
sion
and
hi
stol
ogy
Bow
en’s
dise
ase
Mai
n el
igib
ility
cri
teri
a In
clus
ion
crite
ria:
Patie
nts
18 yr
or
olde
r w
ith
hist
olog
ical
ly c
onfir
med
di
agno
sis
of S
CC
in s
itu
from
a b
iops
y sp
ecim
en
take
n w
ithin
the
last
5 m
th
and
with
no
evid
ence
of
any
chan
ge in
app
eara
nce
sugg
estiv
e of
lesi
on
prog
ress
ion
Lesi
ons
that
had
bee
n tr
eate
d w
ithin
the
pre
viou
s 3
mth
or
that
wer
e st
rong
ly
pigm
ente
d, le
ss t
han
6 m
m
or m
ore
than
40
mm
in
diam
eter
or
loca
ted
on t
he
geni
talia
wer
e ex
clud
edPa
tien
t ch
arac
teri
stic
s Fo
r th
e tr
eate
d pa
tient
s:%
Mal
e: 39
Age
ran
ge: 3
9–99
yrM
ean
age:
73 yr
Loca
tion
of le
sion
(no
. of
lesi
ons)
: fac
e (s
calp
) 68
, ne
ck, t
runk
34,
ext
rem
ities
17
3C
onco
mit
ant
trea
tmen
t N
ot s
tate
d
Tria
l tre
atm
ents
MA
L–PD
T v
s Pl
aceb
o PD
T
vs C
ryot
hera
py v
s 5-
FUIn
terv
enti
on M
AL–
PDT:
Les
ions
wer
e pr
epar
ed b
y ge
ntle
sur
face
deb
ride
men
t w
ith
a cu
rett
e. 1
60 m
g/g
of t
opic
al M
AL
crea
m w
as
appl
ied
to t
he le
sion
s. It
rem
aine
d on
the
ski
n fo
r 3
hr t
hen
was
was
hed
off w
ith 0
.9%
sal
ine
solu
tion
befo
re il
lum
inat
ion
with
non
-coh
eren
t re
d lig
ht. W
avel
engt
h w
as 5
70–6
70 n
m, l
ight
do
se w
as 7
5 J/c
m2 .
Mea
n ill
umin
atio
n tim
e w
as
10 m
in 3
7 s.
Trea
tmen
t w
as r
epea
ted
once
afte
r 1
wk
for
a co
mpl
ete
trea
tmen
t cy
cle.
Les
ions
w
ith a
PR
at
12 w
k w
ere
re-t
reat
edC
ompa
rato
r Pl
aceb
o cr
eam
: As
for
MA
L–PD
T. Le
sion
s w
ith a
PR
at
12 w
k w
ere
re-
trea
ted
2nd
com
para
tor
Cry
othe
rapy
: A h
andh
eld
liqui
d ni
trog
en s
pray
was
use
d in
a s
ingl
e fr
eeze
–tha
w c
ycle
. Afte
r an
initi
al ic
e fie
ld
form
atio
n w
ith a
2-m
m r
im o
f clin
ical
ly h
ealth
y tis
sue,
the
ice
field
was
mai
ntai
ned
for
a m
inim
um o
f 20
s. M
ean
tota
l fre
ezin
g tim
e w
as
25 s
Lesi
ons
with
a P
R a
t 12
wk
wer
e re
-tre
ated
3rd
com
para
tor
5-FU
: Top
ical
5%
5-F
U
crea
m w
as a
pplie
d fo
r 4
wk,
once
dai
ly d
urin
g th
e 1s
t w
eek,
and
twic
e da
ily t
here
afte
r. M
ean
num
ber
of a
pplic
atio
ns w
as 4
2 an
d 45
in t
he
1st
and
2nd
trea
tmen
ts, r
espe
ctiv
ely.
Lesi
ons
with
a P
R a
t 12
wk
wer
e re
-tre
ated
Mor
bidi
ty C
R r
ate
at 3
mth
: PD
T, 10
3/11
1 (9
3%);
Plac
ebo,
4/1
9 (2
1%);
Cry
othe
rapy
, 73/
85 (
86%
), an
d 5-
FU
24/2
9, (
83%
). 12
-mth
rec
urre
nce
rate
: PD
T, 15
%; P
lace
bo, n
ot s
tate
d;
Cry
othe
rapy
, 24%
and
5-F
U, 2
1%.
Estim
ated
sus
tain
ed C
R r
ate
at
12 m
th: P
DT,
80%
; Pla
cebo
, not
st
ated
; cry
othe
rapy
, 67%
; 5-F
U, 6
9%.
The
re w
as a
sta
tistic
ally
sig
nific
ant
diffe
renc
e be
twee
n M
AL–
PDT
an
d co
mbi
ned
stan
dard
the
rapy
(O
R =
1.7
3; 9
5% C
I 1.0
3 to
2.9
3).
MA
L–PD
T w
as s
igni
fican
tly d
iffer
ent
from
cry
othe
rapy
(O
R =
1.7
7 to
1.0
1,
3.12
). Es
timat
ed s
usta
ined
CR
rat
e at
24
mth
: PD
T, 68
%; p
lace
bo, 1
1%;
cryo
ther
apy,
60%
; 5-F
U, 5
9%Q
oL a
nd r
etur
n to
nor
mal
ac
tivi
ty G
ood
or e
xcel
lent
cos
met
ic
outc
ome
at 3
mth
: PD
T, 77
/82
(94%
); cr
yoth
erap
y, 43
/65
(66%
); 5-
FU, 1
6/21
(7
6%). T
his
was
mai
ntai
ned
at 1
2 m
thA
Es
SAEs
: PD
T, 6%
, cry
othe
rapy
, 12%
. SA
Es (
incl
udin
g fo
ur d
eath
s) w
ere
repo
rted
. PD
T, fo
ur p
atie
nts;
plac
ebo
crea
m, t
wo
patie
nts;
cryo
ther
apy,
thre
e pa
tient
s
Aut
hors
’ con
clus
ions
MA
L–PD
T
is a
n ef
fect
ive
trea
tmen
t op
tion
for
Bow
en’s
dise
ase
with
exc
elle
nt
cosm
etic
out
com
eB
rief
stu
dy a
ppra
isal
The
au
thor
s’ c
oncl
usio
ns a
ppea
r ap
prop
riat
e, a
lthou
gh m
itiga
ting
fact
ors
incl
ude
the
fact
tha
t 11
%
of t
reat
ed le
sion
s w
ere
excl
uded
fr
om t
he p
er-p
roto
col p
opul
atio
n,
the
lack
of r
epor
ting
on m
etho
ds
of r
ando
mis
atio
n an
d al
loca
tion
conc
ealm
ent,
and
the
poss
ibili
ty
of in
stitu
tiona
l diff
eren
ces
and
prot
ocol
dev
iatio
n (4
0 ce
ntre
s in
11
cou
ntri
es)
affe
ctin
g re
sults
Appendix 14
222
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
223Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Pui
zina
-Iv
ic e
t al. (
2008
)57
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry C
roat
iaLa
ngua
ge E
nglis
hSt
udy
desi
gn R
CT
No.
of
part
icip
ants
Tota
l: 15
Inte
rven
tion:
Nin
eC
ompa
rato
r: Si
xN
o. o
f rec
ruit
ing
cent
res
One
Follo
w-u
p pe
riod
an
d fr
eque
ncy
24 w
k
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
lesi
on
and
hist
olog
y Bo
wen
’s di
seas
eM
ain
elig
ibili
ty
crit
eria
Pre
viou
s hi
stol
ogic
ally
co
nfirm
ed d
iagn
osis
of
Bow
en’s
dise
ase
Pati
ent
char
acte
rist
ics
Not
st
ated
Tria
l tre
atm
ents
ALA
–PD
T w
ith 1
6-hr
incu
batio
n an
d tw
o lig
ht fr
actio
ns v
s ALA
–PD
T w
ith 5
-hr
incu
batio
n an
d a
sing
le
illum
inat
ion
Inte
rven
tion
ALA
–PD
T w
ith 1
6-hr
incu
batio
n an
d tw
o lig
ht
frac
tions
: Thi
ck c
rust
s w
ere
1st
rem
oved
with
oin
tmen
ts (
and
wet
dre
ssin
gs).
Afte
r cl
eani
ng t
he a
rea
with
a s
alin
e so
lutio
n, t
he
20%
ALA
cre
am w
as a
pplie
d to
a t
hick
ness
of a
ppro
xim
atel
y 1
mm
, cov
erin
g th
e tr
eate
d ar
ea a
nd 1
cm o
f the
sur
roun
ding
sk
in. T
he a
rea
was
cov
ered
by
occl
usiv
e dr
essi
ng. A
lum
iniu
m
foil
was
pla
ced
on t
op in
ord
er t
o pr
otec
t sk
in fr
om a
mbi
ent
light
. The
re w
as t
hen
a 16
-hr
incu
batio
n pe
riod
bef
ore
red
light
(6
35 n
m)
was
app
lied.
The
tot
al o
f 100
J/cm
2 was
del
iver
ed in
tw
o do
ses
of 5
0 J/c
m2 w
ith a
flue
nce
inte
nsity
of 3
0 m
W/c
m2 . T
here
w
as a
2-h
r br
eak
betw
een
illum
inat
ions
. Spr
ayin
g of
wat
er a
nd
cool
ing
with
fan
was
don
e to
min
imis
e pa
in s
ensa
tions
. Afte
r th
e tr
eatm
ents
sun
bloc
k oi
ntm
ents
wer
e re
com
men
ded
for
the
next
fe
w d
ays
in a
dditi
on t
o su
n pr
otec
tion
mea
sure
s. Bi
opsi
es w
ere
perf
orm
ed 2
4 w
k af
ter
illum
inat
ion
in p
atie
nts
with
fluo
resc
ence
de
tect
ed a
fter
4 hr
Com
para
tor
PDT
with
5 h
r in
cuba
tion
with
ALA
cre
am a
nd
sing
le li
ght
frac
tion:
Pre
para
tion
for
illum
inat
ion
was
as
for
the
inte
rven
tion
grou
p. T
here
was
the
n a
5-hr
incu
batio
n pe
riod
be
fore
red
ligh
t (6
35 n
m)
was
app
lied.
100
J/cm
2 was
del
iver
ed
in o
ne d
ose,
with
a fl
uenc
e in
tens
ity o
f 30
mW
/cm
2 . Sp
rayi
ng o
f w
ater
and
coo
ling
with
fans
, and
sun
pro
tect
ion
mea
sure
s w
ere
as fo
r th
e in
terv
entio
n gr
oup.
Biop
sies
wer
e pe
rfor
med
24
wk
afte
r ill
umin
atio
n in
pat
ient
s w
hom
fluo
resc
ence
afte
r 3-
hr
incu
batio
n w
ith A
LA w
as d
etec
ted
Mor
bidi
ty A
t 24
wk,
resi
dual
tum
our
was
fo
und
in fo
ur o
f six
(6
7%)
biop
sied
pat
ient
s in
the
sin
gle-
illum
inat
ion,
sh
orte
r-in
cuba
tion
grou
p. Tr
eatm
ent
was
re
peat
ed. A
t 24
wk,
ther
e w
as p
ersi
sten
ce o
f tu
mou
r in
tw
o of
nin
e (2
2%)
biop
sied
pat
ient
s in
the
frac
tiona
ted,
lo
nger
incu
batio
n gr
oup
QoL
and
ret
urn
to
norm
al a
ctiv
ity
Not
as
sess
edA
Es
Not
ass
esse
d
Aut
hors
’ con
clus
ions
PD
T d
eliv
ered
as
frac
tiona
ted
illum
inat
ion
with
16
hr
of in
cuba
tion
sepa
rate
d by
a 2
-hr
dark
inte
rval
sig
nific
antly
impr
oves
th
erap
eutic
out
com
e in
tum
our
erad
icat
ion
Bri
ef s
tudy
app
rais
al T
his
tria
l ha
d on
ly a
sm
all n
umbe
r of
pat
ient
s w
ith B
owen
’s di
seas
e. P
roce
dure
s of
ran
dom
isat
ion
and
blin
ding
of
outc
ome
asse
ssor
s w
ere
uncl
ear.
No
patie
nt d
etai
ls w
ere
prov
ided
. Alth
ough
th
e gr
oup
rece
ivin
g fr
actio
nate
d ill
umin
atio
n ha
d be
tter
out
com
es, t
he
rela
tive
cont
ribu
tion
of t
he lo
nger
in
cuba
tion
time
and
the
frac
tiona
ted
deliv
ery
are
uncl
ear.
It is
als
o un
clea
r if
ther
e w
ere
any
AEs
Appendix 14
224
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
225Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Sal
im e
t al
. (20
03)72
Link
ed
Publ
icat
ions
185
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry U
KLa
ngua
ge E
nglis
hSt
udy
desi
gn
RC
TN
o. o
f pa
rtic
ipan
tsTo
tal:
40In
terv
entio
n: 2
0 (3
3 le
sion
s)C
ompa
rato
r: 20
(3
3 le
sion
s)N
o. o
f rec
ruit
ing
cent
res
Two
Follo
w-u
p pe
riod
an
d fr
eque
ncy
12 m
th
Type
(s)
of le
sion
and
hi
stol
ogy
Bow
en’s
dise
ase
Mai
n el
igib
ility
cr
iter
ia P
atie
nts
with
1–
3 le
sion
s of
pre
viou
sly
untr
eate
d, h
isto
logi
cally
pr
oven
Bow
en’s
dise
ase
mea
suri
ng 0
.5–4
cmPa
tien
t ch
arac
teri
stic
s%
Mal
e: 20
Age
ran
ge: 6
5–88
yr
Mea
n ag
e: 76
yrLe
sion
site
: Leg
s 58
, arm
s 4,
face
4Pa
tient
s ha
d be
twee
n on
e an
d th
ree
lesi
ons
and
wer
e of
ski
n ty
pes
I–III
Con
com
itan
t tr
eatm
ent
Loca
l an
aest
hetic
(1%
pla
in
lidoc
aine
by
intr
ader
mal
in
ject
ion)
was
offe
red
to p
atie
nts
expe
rien
cing
pa
in d
urin
g PD
T
trea
tmen
t
Tria
l tre
atm
ents
PD
T v
s 5-
FUIn
terv
enti
on 2
0% A
LA in
an
oil-
in-w
ater
em
ulsi
on w
as
appl
ied
to le
sion
s in
clud
ing
a 5-
mm
mar
gin
of c
linic
ally
no
rmal
ski
n 4-
hr b
efor
e PD
T. Ill
umin
atio
n w
as w
ith a
300
-W
xen
on la
mp
at a
dos
e of
100
J/cm
squ
ared
with
a
dens
ity o
f 50–
90 m
W/c
m
squa
red
narr
owba
nd r
ed li
ght
(630
± 1
5 nm
). The
tim
e of
ill
umin
atio
n w
as d
epen
dent
on
lesi
on s
ize
and
rang
ed fr
om
12 t
o 40
min
. All
patie
nts
wer
e re
view
ed a
t 6
wk
and
PDT
was
re
peat
ed if
req
uire
d. F
urth
er
PDT
par
amet
ers
wer
e no
t re
port
edC
ompa
rato
r 5-
FU (
Efud
ix)
was
app
lied
thin
ly t
o th
e le
sion
s in
itial
ly o
nce
daily
dur
ing
wk
1 an
d th
en t
wic
e da
ily (
wk
2–4)
. A
ll pa
tient
s w
ere
revi
ewed
at
6wk
and
5-FU
was
rep
eate
d if
requ
ired
Mor
bidi
ty 2
9 of
33
lesi
ons
(88%
) sh
owed
initi
al c
ompl
ete
clin
ical
cle
aran
ce w
ith P
DT
with
a P
R in
the
four
rem
aini
ng
lesi
ons.
22 o
f 33
lesi
ons
(67%
) ha
d co
mpl
ete
clin
ical
cle
aran
ce
afte
r 5-
FU a
nd s
ix h
ad P
R. F
ive
lesi
ons
wer
e w
ithdr
awn
prio
r to
com
plet
ion
of a
sin
gle
cycl
e of
5-F
U. A
fter
adju
stm
ent
for
the
influ
ence
of l
esio
n si
ze o
n re
spon
se, t
he d
iffer
ence
in
cle
aran
ce r
ates
was
NS.
At
12 m
th F
U t
here
wer
e tw
o re
curr
ence
s in
the
PD
T g
roup
(at
6 a
nd 7
mth
). The
re w
ere
six
recu
rren
ces
in t
he 5
-FU
gro
up (
at 5
, 7, 8
, 11
and
2 at
12
mth
). O
vera
ll cl
eara
nce
(at
12 m
th)
in t
he P
DT
gro
up w
as 2
7 of
33
lesi
ons
(82%
) vs
16
of 3
3 le
sion
s in
the
5-F
U g
roup
(48
%).
OR
= 4
.78
(95%
CI 1
.56
to 1
4.62
, p =
0.0
06)
QoL
and
ret
urn
to n
orm
al a
ctiv
ity
Not
ass
esse
dA
Es T
hree
pat
ient
s w
ith fi
ve le
sion
s fr
om t
he 5
-FU
gro
up
deve
lope
d w
ides
prea
d de
rmat
itic
reac
tions
ove
r th
e tr
eate
d lim
bs a
nd w
ere
with
draw
n fr
om t
he s
tudy
. Ano
ther
pat
ient
w
ith t
wo
lesi
ons
from
the
5-F
U g
roup
had
wid
espr
ead
derm
atiti
c re
actio
ns b
ut e
lect
ed t
o co
ntin
ue t
he t
reat
men
t. In
the
5-F
U g
roup
, thr
ee le
sion
s ul
cera
ted
and
two
deve
lope
d pa
infu
l ero
sion
s on
com
plet
ion
of t
he t
reat
men
t cy
cle.
The
ul
cera
ted
lesi
ons
heal
ed le
avin
g pr
omin
ent
scar
ring
. The
re
wer
e no
rea
ctio
ns in
the
PD
T g
roup
and
no
clin
ical
ly o
bvio
us
scar
form
atio
n at
12
mth
at
any
PDT
tre
atm
ent
site
. 10
of 1
5 pa
tient
s in
the
5-F
U g
roup
and
14
of 1
9 in
the
PD
T g
roup
re
port
ed p
ain
duri
ng t
he t
reat
men
t cy
cle.
Dur
ing
PDT
pai
n w
as r
ated
‘mild
’ by
six
patie
nts,
‘mod
erat
e’ b
y si
x an
d ‘s
ever
e’
by t
wo.
Pai
n se
ttle
d fo
llow
ing
illum
inat
ion
in 4
pat
ient
s an
d pe
rsis
ted
to 2
4 hr
in fo
ur. M
ild d
isco
mfo
rt w
as r
epor
ted
by t
he
rem
aini
ng s
ix p
atie
nts
last
ing
7–42
d (
mea
n 14
). In
the
5-F
U
grou
p pa
in w
as r
ated
‘mild
’ by
six
patie
nts,
‘mod
erat
e’ b
y tw
o an
d ‘s
ever
e’ b
y tw
o. D
isco
mfo
rt p
ersi
sted
in t
he 5
-FU
gro
up
for
7–42
d (
mea
n 21
). In
ass
essm
ent
of in
tens
ity a
nd d
urat
ion
of p
ain,
mor
e pa
in w
as fo
und
in t
he 5
-FU
gro
up (
p =
0.01
). C
ompa
riso
n of
tot
al p
ain
over
tim
e re
veal
ed n
o st
atis
tical
ly
sign
ifica
nt d
iffer
ence
in t
he m
edia
n pa
in s
core
s be
twee
n th
e tw
o gr
oups
Aut
hors
’ con
clus
ions
Top
ical
A
LA–P
DT
is m
ore
effe
ctiv
e th
an
topi
cal 5
-FU
in t
he t
reat
men
t of
Bow
en’s
dise
ase
with
few
er
AEs
. ALA
sho
uld
be c
onsi
dere
d on
e of
the
1st
-line
the
rape
utic
op
tions
for
Bow
en’s
dise
ase
Bri
ef s
tudy
app
rais
al
Met
hods
of r
ando
mis
atio
n,
allo
catio
n co
ncea
lmen
t an
d bl
indi
ng o
f out
com
e as
sess
ors
wer
e no
t de
scri
bed.
Thi
s st
udy,
alth
ough
sm
all,
high
light
s th
e po
tent
ial o
f PD
T fo
r Bo
wen
’s di
seas
e bu
t re
sults
sho
uld
be
confi
rmed
in fu
rthe
r tr
ials
Appendix 14
224
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
225
Appendix 15 Basal cell carcinoma data extraction
Appendix 15
226
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
227Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Bas
sett
-Se
guin
et a
l. (20
08)79
Link
ed
publ
icat
ions
186–
190
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry N
ot s
tate
dLa
ngua
ge E
nglis
hSt
udy
desi
gn R
CT
(b
etw
een-
part
icip
ant
com
pari
son)
No.
of p
arti
cipa
nts
Tota
l: 12
0 ra
ndom
ised
, 11
8 tr
eate
d (2
19
lesi
ons)
Inte
rven
tion:
60,
58
trea
ted
and
anal
ysed
(1
03 le
sion
s)C
ompa
rato
r: 58
, 57
trea
ted
and
anal
ysed
(9
8 le
sion
s)N
o. o
f rec
ruit
ing
cent
res
13 a
cros
s se
ven
Euro
pean
co
untr
ies
Follo
w-u
p pe
riod
an
d fr
eque
ncy
3 m
th, t
hen
at 1
, 2, 3
, 4
and
5 yr
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y Pr
imar
y su
perfi
cial
BC
CM
ain
elig
ibili
ty
crit
eria
Pat
ient
s ag
ed
18 yr
or
olde
r w
ith
up t
o 10
pre
viou
sly
untr
eate
d pr
imar
y su
perfi
cial
BC
C
lesi
ons
suita
ble
for
cryo
ther
apy.
Dia
gnos
is
confi
rmed
usi
ng p
unch
bi
opsy
. Les
ions
had
to
have
dia
met
er >
6 m
m
but
< 15
mm
on
face
/sc
alp,
< 20
mm
on
neck
/ex
trem
ities
, or
< 30
mm
on
tru
nk. F
urth
er
elig
ibili
ty c
rite
ria
wer
e re
port
edPa
tien
t ch
arac
teri
stic
s N
ot
stat
edC
onco
mit
ant
trea
tmen
t C
onco
mita
nt
trea
tmen
t w
ith
imm
unos
uppr
essi
ve
med
icat
ion
was
pr
ohib
ited
Tria
l tre
atm
ents
MA
L–PD
T
vs C
ryot
hera
pyIn
terv
enti
on M
AL–
PDT:
A
sing
le t
reat
men
t w
as in
itial
ly
give
n. L
esio
ns w
ere
prep
ared
by
sur
face
deb
ride
men
t. M
AL
crea
m, 1
60 m
g/g,
was
ap
plie
d in
a la
yer
of 1
mm
to
the
lesi
on a
nd 5
mm
of
surr
ound
ing
tissu
e fo
r 3
hr. T
he
crea
m w
as w
ashe
d of
f usi
ng a
sa
line
solu
tion
and
the
trea
ted
area
was
the
n ill
umin
ated
w
ith n
on-c
oher
ent
red
light
(w
avel
engt
h 57
0–67
0 nm
) us
ing
a lig
ht d
ose
of 7
5 J/c
m.
In p
atie
nts
with
inco
mpl
ete
CR
at
3-m
th t
reat
men
t w
as
repe
ated
(tw
o co
nsec
utiv
e M
AL–
PDT
ses
sion
s 7
d ap
art)
Com
para
tor
Cry
othe
rapy
: C
ryot
hera
py w
as a
pplie
d in
tw
o fr
eeze
–tha
w c
ycle
s us
ing
liqui
d ni
trog
en s
pray
ap
plie
d to
the
lesi
on a
nd a
3-
mm
sur
roun
ding
are
a of
he
alth
y tis
sue.
Pro
cedu
re w
as
repe
ated
afte
r a
thaw
per
iod
of t
wo
to t
hree
tim
es t
he
free
ze d
urat
ion.
In p
atie
nts
with
an
inco
mpl
ete
resp
onse
at
3-m
th t
reat
men
t w
as
repe
ated
(do
uble
free
ze–t
haw
cr
yoth
erap
y)
Mor
bidi
ty3
mth
(11
5 pa
tient
s): L
esio
ns w
ith in
CR
afte
r 3
mth
wer
e 32
% in
th
e PD
T g
roup
and
30%
in t
he c
ryot
hera
py g
roup
. CR
rat
es d
id
not
diffe
r be
twee
n th
e gr
oups
(PD
T: 9
7% v
s cr
yoth
erap
y: 95
%,
p =
0.49
)12
mth
(10
5 pa
tient
s): F
ewer
lesi
ons
recu
rred
with
MA
L–PD
T
than
with
cry
othe
rapy
(8%
vs
16%
) M
ore
patie
nts
had
an
‘exc
elle
nt/g
ood’
cos
met
ic o
utco
me
with
MA
L–PD
T t
han
with
cr
yoth
erap
y at
3 a
nd 1
2 m
th36
mth
(10
7 pa
tient
s): P
ropo
rtio
n of
lesi
ons
in C
R w
as 6
6% fo
r M
AL–
PDT
and
67%
for
cryo
ther
apy
(NS)
. 74%
est
imat
ed C
R
rate
in b
oth
grou
ps a
ccor
ding
to
per-
prot
ocol
pop
ulat
ion.
The
le
sion
rec
urre
nce
rate
s in
lesi
ons
with
CR
3 m
th a
fter
the
last
tr
eatm
ent
wer
e 23
% fo
r M
AL–
PDT
and
20%
for
cryo
ther
apy
The
ove
rall
cosm
etic
out
com
e w
as r
ated
by
phys
icia
ns a
s ‘e
xcel
lent
’ or ‘
good
’ for
89%
of t
he M
AL–
PDT
pat
ient
s an
d 63
%
of t
he c
ryot
hera
py p
atie
nts
5 yr
: CR
rat
es d
id n
ot d
iffer
bet
wee
n th
e gr
oups
(PD
T: 7
5% v
s cr
yoth
erap
y: 74
%, p
= 0
.90)
. Cum
ulat
ive
recu
rren
ce r
ate
afte
r 5
yr w
as P
DT:
22%
and
cry
othe
rapy
: 20%
, p =
0.8
6Q
oL a
nd r
etur
n to
nor
mal
act
ivit
y C
osm
etic
out
com
e w
as b
ette
r w
ith P
DT
at
both
3 m
th a
nd 5
yr 3
mth
: 30%
of P
DT
pa
tient
s ha
d an
‘exc
elle
nt’ o
utco
me
com
pare
d w
ith 4
% fo
r cr
yoth
erap
y (p
= 0
.000
5)5
yr: 6
0% o
f PD
T p
atie
nts
had
an ‘e
xcel
lent
’ out
com
e co
mpa
red
with
16%
for
cryo
ther
apy
(p =
0.0
0078
)A
ll co
smet
ic o
utco
mes
rat
ed b
y in
vest
igat
ors
usin
g a
4-po
int
scal
eA
Es A
Es w
ere
repo
rted
by
73%
(44
/60)
PD
T p
atie
nts
and
79%
(4
6/58
) cr
yoth
erap
y pa
tient
s. M
ost A
Es w
ere
loca
l and
tra
nsie
nt,
no p
atie
nts
disc
ontin
ued
as a
res
ult
of t
reat
men
t-re
late
d A
EsPa
in: 3
7% P
DT,
33%
cry
othe
rapy
Cru
stin
g: 35
% P
DT,
47%
cry
othe
rapy
Eryt
hem
a: 30
% P
DT,
21%
cry
othe
rapy
Mild
: 80%
PD
T 7
3% c
ryot
hera
pyM
oder
ate:
13%
PD
T, 25
% c
ryot
hera
pySe
vere
: 5%
PD
T, 1%
cry
othe
rapy
Aut
hors
’ con
clus
ions
Thi
s st
udy
dem
onst
rate
d th
at le
sion
re
curr
ence
rat
e w
ith M
AL–
PDT
tr
eatm
ent
was
com
para
ble
to
doub
le fr
eeze
tha
w c
ryot
hera
py
for
trea
tmen
t of
sup
erfic
ial B
CC
an
d pr
ovid
ed a
bet
ter
cosm
etic
ou
tcom
eB
rief
stu
dy a
ppra
isal
Ove
rall
this
tri
al w
as w
ell c
ondu
cted
cl
earl
y re
port
ed. T
he la
ck o
f a
pow
er c
alcu
latio
n m
eans
it
is u
ncle
ar if
the
re w
as
no d
iffer
ence
bet
wee
n th
e tr
eatm
ents
, or
if th
e st
udy
was
un
derp
ower
ed t
o de
tect
suc
h a
diffe
renc
e. T
his
tria
l did
incl
ude
a lo
ng t
erm
FU
of 5
yr a
s w
ell
as e
xam
inat
ion
of s
afet
y, ef
ficac
y an
d co
smet
ic o
utco
mes
Appendix 15
226
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
227Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Ber
roet
a et
al.
(200
7)87
Link
ed p
ublic
atio
ns19
1
Dat
a so
urce
Ful
l pub
lishe
d pa
per
(lett
er)
Cou
ntry
UK
Lang
uage
Eng
lish
Stud
y de
sign
RC
T
(bet
wee
n-pa
rtic
ipan
t co
mpa
riso
n)N
o. o
f par
tici
pant
sTo
tal:
31 (
40 le
sion
s)In
terv
entio
n: 1
8 (2
1 le
sion
s)C
ompa
rato
r: 13
(19
lesi
ons)
No.
of r
ecru
itin
g ce
ntre
s O
neFo
llow
-up
peri
od a
nd
freq
uenc
y FU
to
asse
ss
resp
onse
at
3, 6
and
12
mth
. FU
to
asse
ss p
ain
at 3
, 6, 2
4 an
d 48
hr
and
also
at
1 w
k
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y N
odul
ar B
CC
Mai
n el
igib
ility
cr
iter
ia N
on-
preg
nant
adu
lts (
18
or o
ver)
with
wel
l-de
fined
BC
Cs ≤
2cm
on
ana
tom
ical
ly n
on-
criti
cal s
ites
wer
e el
igib
lePa
tient
s w
ith
recu
rren
t BC
Cs,
or
BCC
s at
hig
h-ri
sk
site
s or
pat
ient
s w
ith
imm
unod
efici
ency
or
phot
osen
sitiv
ity w
ere
excl
uded
% M
ale:
100
Con
com
itan
t tr
eatm
ent
Not
st
ated
Tria
l tre
atm
ents
ALA
–PD
T (
follo
win
g su
perfi
cial
cur
etta
ge)
vs E
xcis
ion
surg
ery
Inte
rven
tion
Initi
al 4
-mm
pun
ch
biop
sy t
o as
sess
tum
our
dept
h, fo
llow
ed
by s
uper
ficia
l cur
etta
ge (
with
out
anae
sthe
tic)
and
PDT
with
630
-nm
lase
r af
ter
20%
ALA
app
lied
for
6 hr
(un
der
occl
usio
n). I
rrad
ianc
e w
as 1
2 m
W/c
m2
and
tota
l dos
e 12
5 J/c
m2 .
PDT
rep
eate
d at
3 m
th if
res
idua
l BC
C w
as c
linic
ally
ev
iden
tC
ompa
rato
r Ex
cisi
on w
ith s
urgi
cal
mar
gins
as
reco
mm
ende
d by
the
Bri
tish
Ass
ocia
tion
of D
erm
atol
ogis
ts. S
calp
el
surg
ery
was
per
form
ed u
nder
infil
trat
ive
lidoc
aine
ana
esth
esia
but
sur
gica
l re-
exci
sion
s w
ere
not
cond
ucte
d
Mor
bidi
ty F
or t
he P
DT
gro
up 1
3/21
le
sion
s (6
2%)
wer
e cl
ear
at 1
yr
com
pare
d to
15/
19 le
sion
s (7
9%)
in t
he
surg
ery
grou
p, p
= 0.
24T
here
wer
e fiv
e pe
rsis
tent
BC
Cs
in
the
PDT
gro
up b
ut n
one
in t
he s
urge
ry
grou
p (n
s)Q
oL a
nd r
etur
n to
nor
mal
act
ivit
y T
here
was
no
diffe
renc
e in
mea
n sc
ar
seve
rity
(on
a 1
–4 s
cale
) be
twee
n th
e gr
oups
whe
n ju
dged
inde
pend
ently
by
10 n
on-m
edic
al m
en (
1.9
for
PDT
vs
2.1
for
surg
ery,
p =
0.42
) or
10
non-
med
ical
w
omen
(2.
2 fo
r PD
T v
s 2.
5 fo
r su
rger
y, p
= 0.
23)
AE
s M
edia
n pa
in s
core
s fo
r th
e 1s
t BC
C t
reat
ed (
scor
ed o
ut o
f 10)
bot
h du
ring
tre
atm
ent,
and
imm
edia
tely
afte
r tr
eatm
ent,
wer
e fiv
e fo
r th
e PD
T g
roup
, an
d 0
for
surg
ery
grou
p (p
= 0
.001
, and
p
= 0.
004,
res
pect
ivel
y). B
oth
grou
ps h
ad
a sc
ore
of z
ero
at la
ter
asse
ssm
ents
Aut
hors
’ con
clus
ions
The
re w
as n
o su
gges
tion
that
PD
T w
as, i
n ge
nera
l, be
tter
tha
n su
rger
y. PD
T a
ppea
rs m
ore
pain
ful t
han
surg
ery
for
low
-ris
k nB
CC
s. Su
rger
y re
mai
ns t
he 1
st t
reat
men
t ch
oice
for
nBC
Cs
Bri
ef s
tudy
app
rais
al T
his
smal
l pilo
t st
udy
was
gen
eral
ly o
f hig
h qu
ality
in it
s m
etho
ds a
nd r
epor
ting.
The
abs
ence
of
anae
sthe
tic fo
r th
e PD
T g
roup
bef
ore
cure
ttag
e m
ay e
xpla
in t
he d
iffer
ence
s in
pa
in s
core
s
Appendix 15
228
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
229Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
de
Haa
s et
al.
(200
6)83
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry T
he
Net
herl
ands
Lang
uage
Eng
lish
Stud
y de
sign
RC
T
(bet
wee
n-pa
rtic
ipan
t co
mpa
riso
n)N
o. o
f par
tici
pant
sTo
tal:
154
(505
lesi
ons)
Inte
rven
tion:
55
(262
le
sion
s)C
ompa
rato
r: 10
0 (2
43
lesi
ons)
No.
of r
ecru
itin
g ce
ntre
s O
neFo
llow
-up
peri
od a
nd
freq
uenc
y FU
four
tim
es
a ye
ar in
1st
yea
r, th
en
twic
e ye
arly.
Pat
ient
s te
ndin
g to
dev
elop
mor
e le
sion
s w
ere
seen
mor
e fr
eque
ntly.
Min
imum
FU
pe
riod
was
1 yr
, max
imum
FU
per
iod
was
5 yr
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y Pr
imar
y su
perfi
cial
BC
CM
ain
elig
ibili
ty
crit
eria
Not
sta
ted
Pati
ent
char
acte
rist
ics A
ge
rang
e: 31
–83
yrM
ean
age:
57 yr
All
part
icip
ants
wer
e C
auca
sian
sC
onco
mit
ant
trea
tmen
t Pa
race
tam
ol, l
idoc
aine
(w
ithou
t ad
rena
line)
or
bup
ivac
aine
if
requ
ired
Tria
l tre
atm
ents
Fra
ctio
nate
d ill
umin
atio
n PD
T v
s si
ngle
-illu
min
atio
n PD
TIn
terv
enti
on F
ract
iona
ted
illum
inat
ion
PDT:
Cru
sts
and
scal
ing
wer
e ge
ntly
rem
oved
us
ing
a di
spos
able
cur
ette
bef
ore
ALA
ap
plic
atio
n. Il
lum
inat
ion
usin
g do
ses
of 2
0 an
d 80
J/cm
2 (at
50
mW
/cm
2 ) d
eliv
ered
4 a
nd 6
hr
afte
r ad
min
istr
atio
n of
20%
ALA
oin
tmen
t (c
onta
inin
g 2%
lido
cain
e) w
ith a
1-c
m m
argi
n.
One
of t
hree
diff
eren
t lig
ht s
ourc
es w
ere
used
on
each
lesi
on (
a 63
0-nm
dio
de la
ser,
coup
led
into
a 6
00-µ
m o
ptic
al fi
bre
and
usin
g a
com
bina
tion
of le
nses
for
unifo
rm fl
uenc
e ra
te;
a lig
ht-e
mitt
ing
diod
e 63
3 nm
with
a b
andw
idth
of
20
nm; o
r a
2nd
broa
dban
d so
urce
with
an
out
put
of b
etw
een
590
and
650
nm),
with
a
mar
gin
of a
t le
ast
5 m
m. A
ligh
t-pr
otec
tive
band
age
(incl
udin
g al
umin
ium
foil)
was
use
d to
pro
vide
the
2-h
r da
rk in
terv
al b
etw
een
frac
tions
. Par
ticip
ants
wer
e in
stru
cted
to
stay
ou
t of
the
col
dC
ompa
rato
r PD
T w
ith p
lace
bo c
ream
: Pa
tient
s re
ceiv
ed t
wo
cycl
es (
1 w
k ap
art)
of
pla
cebo
cre
am P
DT.
The
re w
as s
urfa
ce
debr
idem
ent
and
slig
ht le
sion
deb
ulki
ng p
rior
to
PD
T. BC
C w
ith p
artia
l clin
ical
res
pons
e at
3
mth
wer
e re
-tre
ated
. Fur
ther
par
amet
ers
wer
e no
t re
port
ed
Mor
bidi
ty C
R o
f les
ions
w
as s
igni
fican
tly g
reat
er u
sing
fr
actio
nate
d ill
umin
atio
n co
mpa
red
with
sin
gle
illum
inat
ion
(at
1 yr
, 97
% v
s 89
%, p
= 0
.002
). The
res
ults
w
ere
very
sim
ilar
whe
n an
alys
is
was
und
erta
ken
on a
sub
grou
p of
hi
stol
ogic
ally
pro
ven
BCC
s. 10
/262
(4
%)
lesi
ons
faile
d to
res
pond
, or
rec
urre
d, in
the
frac
tiona
ted-
illum
inat
ion
grou
p co
mpa
red
with
32/
243
(13%
) in
the
sin
gle-
illum
inat
ion
grou
p (p
= 0
.000
2).
The
re w
ere
no s
igni
fican
t di
ffere
nces
in r
espo
nse
rate
s, w
ithin
ea
ch il
lum
inat
ion
grou
p, fo
r th
e di
ffere
nt li
ght
sour
ces
used
QoL
and
ret
urn
to n
orm
al
acti
vity
Ass
esse
d bu
t no
t re
port
edA
Es
5/10
0 (5
%)
patie
nts
requ
ired
pain
rel
ief i
n th
e si
ngle
illu
min
atio
n gr
oup
com
pare
d to
15/
55 (
27%
) pa
tient
s in
the
frac
tiona
ted
illum
inat
ion
grou
p
Aut
hors
’ con
clus
ions
The
re is
a
sign
ifica
nt in
crea
se in
the
CR
rat
e of
PD
T u
sing
tw
o-lig
ht fr
actio
n ill
umin
atio
n sc
hem
e co
mpa
red
with
a s
ingl
e-ill
umin
atio
n sc
hem
eB
rief
stu
dy a
ppra
isal
Alth
ough
tr
eatm
ent
met
hods
wer
e ve
ry w
ell
desc
ribe
d, s
tudy
des
ign
deta
ils o
n is
sues
su
ch a
s ra
ndom
isat
ion,
blin
ding
, and
dr
opou
ts (
wer
e 15
4 or
155
pat
ient
s tr
eate
d?)
wer
e no
t pr
ovid
ed, m
akin
g it
diffi
cult
to a
sses
s th
e re
liabi
lity
of t
he
resu
lts
Appendix 15
228
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
229Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Fol
ey e
t al. (
2003
)77
Dat
a so
urce
Abs
trac
tC
ount
ry A
ustr
alia
Lang
uage
Eng
lish
Stud
y de
sign
RC
T (
betw
een-
part
icip
ant
com
pari
son)
No.
of p
arti
cipa
nts
Tota
l: 66
Inte
rven
tion:
33
Com
para
tor:
33N
o. o
f rec
ruit
ing
cent
res
Not
sta
ted
Follo
w-u
p pe
riod
and
fr
eque
ncy
Not
cle
ar, b
ut
appe
ared
to
be a
t le
ast
6 m
th
Trea
tmen
t in
tent
ion
Cur
ativ
e pa
tient
s w
ith h
isto
logi
cally
co
nfirm
ed n
BCC
Type
(s)
of c
ance
r an
d hi
stol
ogy
nBC
CM
ain
elig
ibili
ty
crit
eria
Pat
ient
s w
ith h
isto
logi
cally
co
nfirm
ed n
BCC
Pati
ent
char
acte
rist
ics
Not
st
ated
Con
com
itan
t tr
eatm
ent
Not
st
ated
Tria
l tre
atm
ents
PD
T (
met
hyl
amin
olev
ulin
ate)
vs
PDT
(pl
aceb
o cr
eam
)In
terv
enti
on L
esio
ns 1
st p
repa
red
by d
ebri
dem
ent/
debu
lkin
g. PD
T w
ith
160
mg/
g of
met
hyl a
min
olev
ulin
ate
crea
m a
nd 3
hr
of r
ed li
ght
(570
–67
0 nm
) w
ith a
tot
al li
ght
dose
of
75 J/
cm2 . T
reat
men
t re
peat
ed a
fter
7 d.
Le
sion
s w
ith P
R a
t 3
mth
wer
e re
-tr
eate
d. F
urth
er P
DT
par
amet
ers
wer
e no
t re
port
edC
ompa
rato
r As
for
activ
e PD
T g
roup
, bu
t us
ing
plac
ebo
crea
m
Mor
bidi
ty A
t 6
mth
, his
tolo
gica
l ev
alua
tion
ther
e w
ere
no s
igns
of
mal
igna
ncy
in 7
3% o
f the
act
ive
PDT
gr
oup
vs 2
1% in
the
pla
cebo
PD
T g
roup
(p
< 0
.001
)Q
oL a
nd r
etur
n to
nor
mal
act
ivit
y C
osm
etic
out
com
e ra
ted
as e
xcel
lent
or
goo
d in
95%
of t
he a
ctiv
e PD
T
patie
nts
AE
s The
re w
ere
no t
reat
men
t-re
late
d se
riou
s or
sys
tem
ic A
Es.
Burn
ing,
stin
ging
, pai
n, a
nd e
ryth
ema
wer
e tr
ansi
ent,
and
grad
ed a
s m
ild o
r m
oder
ate
Aut
hors
’ con
clus
ions
PD
T is
a
good
alte
rnat
ive
to e
xist
ing
ther
apie
s, pa
rtic
ular
ly in
are
as w
here
an
exce
llent
co
smet
ic o
utco
me
is c
ruci
alB
rief
stu
dy a
ppra
isal
Lim
ited
repo
rtin
g of
met
hods
and
res
ults
mak
es
mea
ning
ful i
nter
pret
atio
n di
fficu
lt. N
o de
tails
wer
e re
port
ed o
n w
ho a
sses
sed
cosm
etic
out
com
es, a
nd w
heth
er
outc
ome
asse
ssor
s w
ere
blin
ded.
O
utco
mes
not
alw
ays
repo
rted
for
both
gro
ups,
or b
roke
n do
wn
by g
roup
nBC
C, n
odul
ar b
asal
cel
l car
cino
ma.
Appendix 15
230
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
231Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Kui
jper
s et
al
. (20
06)84
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry T
he
Net
herl
ands
Lang
uage
Eng
lish
Stud
y de
sign
RC
T
(bet
wee
n-pa
rtic
ipan
t co
mpa
riso
n)N
o. o
f par
tici
pant
sTo
tal:
43 B
CC
s in
39
patie
nts
Inte
rven
tion:
22
BCC
sC
ompa
rato
r: 21
BC
Cs
No.
of r
ecru
itin
g ce
ntre
s O
neFo
llow
-up
peri
od
and
freq
uenc
y 8
wk
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y N
odul
ar p
rim
ary
BCC
Mai
n el
igib
ility
cri
teri
a Pa
tient
s w
ith n
odul
ar p
rim
ary
BCC
loca
ted
anyw
here
on
skin
ex
cept
per
iocu
lar
area
and
hai
ry
scal
p, w
ith a
clin
ical
dia
met
er
smal
ler
than
20
mm
. Pig
men
ted
BCC
s an
d pa
tient
s w
ith m
ore
than
five
BC
Cs
wer
e ex
clud
ed,
as w
ere
patie
nts
with
por
phyr
ia,
cont
rain
dica
tions
to
surg
ery,
or
hype
rsen
sitiv
ity t
o da
ylig
ht o
r to
ei
ther
of t
he c
ream
sPa
tien
t ch
arac
teri
stic
s%
Mal
e: 62
Age
ran
ge: 3
9–87
yrM
ean
age:
68 yr
Mos
t tu
mou
rs w
ere
less
tha
n 10
mm
in d
iam
eter
Con
com
itan
t tr
eatm
ent
Topi
cal e
mol
lient
for
pain
Tria
l tre
atm
ents
PD
T w
ith
5-am
inol
evul
inat
e (A
LA–P
DT
) vs
PD
T
with
met
hyl a
min
olev
ulin
ate
(MA
L–PD
T)
Inte
rven
tion
ALA
–PD
T: A
ll tu
mou
r tis
sue
abov
e sk
in le
vel w
as r
emov
ed
by c
uret
tage
(w
ith e
thyl
chl
orid
e sp
ray
anae
sthe
tic). T
he v
isib
le t
umou
r, pl
us
5-m
m m
argi
n, w
as c
over
ed in
a la
yer
of 2
0% A
LA c
ream
(ar
ound
2 m
m
thic
k) a
nd p
olyu
reth
ane
and
opaq
ue
dres
sing
s w
ere
appl
ied.
Afte
r 3
hr
the
area
was
cle
aned
and
illu
min
ated
w
ith li
ght
of 6
00–7
30 n
m (
from
met
al
halo
gen
sour
ce)
with
an
inte
nsity
of
100
mW
/cm
2 giv
ing
a to
tal d
ose
of
75 J/
cm2 . A
fter
illum
inat
ion
the
area
w
as c
over
ed w
ith a
ligh
t pr
otec
tive
dres
sing
for
1 d
Proc
edur
e re
peat
ed a
fter
7 d
(but
w
ithou
t de
bulk
ing)
Com
para
tor
MA
L–PD
T:
Sam
e m
etho
ds a
s fo
r PD
T w
ith
5-am
inol
evul
inat
e gr
oup,
exce
pt 1
6%
met
hyl a
min
olev
ulin
ate
crea
m w
as
used
inst
ead
of 2
0% A
LA
Mor
bidi
ty T
here
was
no
stat
istic
ally
si
gnifi
cant
diff
eren
ce in
inco
mpl
ete
clea
ranc
e ra
tes
[6/2
2 (2
7%) A
LA v
s 6/
21 (
29%
) M
AL,
p =
0.9
2]Q
oL a
nd r
etur
n to
nor
mal
ac
tivi
ty N
ot a
sses
sed
AE
s Ave
rage
inte
nsity
of p
ain
did
not
diffe
r si
gnifi
cant
ly b
etw
een
grou
ps (
1st
trea
tmen
t: VA
S = 4
.4 fo
r ALA
vs
2.8
for
MA
L, p
= 0
.09,
2nd
tre
atm
ent: V
AS =
4.8
fo
r ALA
vs
3.9
for
MA
L, p
= 0
.4),
nor
did
char
acte
r of
pai
n. M
ost
pain
was
de
scri
bed
as b
eing
bur
ning
or
stin
ging
Aut
hors
’ con
clus
ions
The
stu
dy
foun
d no
diff
eren
ce in
sho
rt-t
erm
ef
ficac
y be
twee
n A
LA–P
DT
and
M
AL–
PDT,
so b
oth
can
be e
qual
ly
reco
mm
ende
d as
pho
tose
nsiti
sers
Bri
ef s
tudy
app
rais
al T
his
pilo
t st
udy
blin
ded
both
pat
ient
s an
d ou
tcom
e as
sess
ors.
How
ever
, the
re
was
no
men
tion
of a
pow
er c
alcu
latio
n an
d th
e sa
mpl
e si
ze w
as v
ery
smal
l; a
larg
er s
tudy
wou
ld h
ave
been
mor
e in
form
ativ
e, p
artic
ular
ly o
n di
ffere
nces
in
pai
n sc
ores
Appendix 15
230
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
231Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Lui
et a
l. (20
04)68
Dat
a so
urce
Ful
l pub
lishe
d pa
per
Cou
ntri
es C
anad
a, U
SALa
ngua
ge E
nglis
hSt
udy
desi
gn R
CT
(be
twee
n-pa
rtic
ipan
t co
mpa
riso
n)N
o. o
f par
tici
pant
sTo
tal:
Not
sta
ted
by d
iagn
osis
(3
87 le
sion
s cl
assi
fied
as B
CC
)In
terv
entio
n: S
uper
ficia
l BC
C
120
lesi
ons;
nBC
C 4
7 le
sion
s; BC
C (
not
spec
ified
) ze
roC
ompa
rato
r: Su
perfi
cial
BC
C
77 le
sion
s; nB
CC
30
lesi
ons;
BCC
(no
t sp
ecifi
ed)
nine
2nd
Com
para
tor:
Supe
rfici
al
BCC
80
lesi
ons;
nBC
C 1
6 le
sion
s, BC
C (
not
spec
ified
) ei
ght
No.
of r
ecru
itin
g ce
ntre
s Fo
urFo
llow
-up
peri
od a
nd
freq
uenc
y FU
at
6 w
k, an
d 3,
6,
12,
18
and
24 m
th (
optio
nal
beyo
nd 6
mth
)
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y Su
perfi
cial
BC
C, 2
77
lesi
ons
(66%
); nB
CC
, 93
lesi
ons
(22%
); Bo
wen
’s di
seas
e, 3
4 le
sion
s (8
%);
BCC
uns
peci
fied
17 le
sion
s (4
%)
Mai
n el
igib
ility
cri
teri
a Pa
tient
s w
ith a
t le
ast
two
biop
sy-
prov
en s
uper
ficia
l or
nBC
C o
r Bo
wen
’s le
sion
sPa
tien
t ch
arac
teri
stic
s N
ot
stat
ed fo
r BC
C o
nly
(stu
dy a
lso
incl
uded
SC
C)
but
over
all:
Ave
rage
tum
ours
tre
ated
per
pa
tient
= e
ight
Age
ran
ge: 2
2–79
yrM
ean
age:
55 yr
Mos
t pa
tient
s ha
d Fi
tzpa
tric
k sk
in
type
II o
r III
Con
com
itan
t tr
eatm
ent
Ora
l an
alge
sic
drug
s fo
r pa
in
Tria
l tre
atm
ents
PD
T a
t 60
J/cm
2 vs
PDT
at
120
J/cm
2 vs
PDT
at
180
J/cm
2
Inte
rven
tion
PD
T a
t 60
J/cm
2 : 10
m
in in
trav
enou
s in
fusi
on o
f 14
mg/
m2
vert
epor
fin, f
ollo
wed
1–3
hr
late
r by
exp
osur
e to
60
J/cm
2 of r
ed li
ght
(688
± 1
0 nm
) fr
om a
non
-the
rmal
LE
D p
anel
. The
exp
osed
are
a in
clud
ed
a m
argi
n of
3–4
mm
aro
und
the
lesi
on. T
he ir
radi
ance
del
iver
ed w
as
200
± 40
mW
/cm
2 . Tum
ours
re-
trea
ted
at 3
mth
if n
eces
sary
(w
ith d
ose
incr
ease
d to
18
mg/
m2 )
Com
para
tor
PDT
at
120
J/cm
2 : Se
e ab
ove
2nd
com
para
tor
PDT
at
180
J/cm
2 : Se
e ab
ove
Mor
bidi
ty A
t 6
mth
, the
hi
stop
atho
logi
cal r
espo
nse
(i.e.
no
resi
dual
tum
our)
was
: nBC
C: 7
6% a
t 60
J/cm
2 , 82
% a
t 12
0 J/c
m2 ,
and
100%
at
180
J/cm
2 ; su
perfi
cial
BC
C: 6
3%, 8
0%,
and
97%
; BC
C n
ot s
peci
fied:
0%
, 56%
an
d 75
%T
here
was
a t
rend
indi
catin
g a
bett
er
resp
onse
with
a h
ighe
r lig
ht d
ose
(p =
0.0
6)Q
oL a
nd r
etur
n to
nor
mal
ac
tivi
ty R
epor
ted
by li
ght
dose
ra
ther
tha
n tu
mou
r ty
peA
Es
Rep
orte
d by
ligh
t do
se, r
athe
r th
an b
y tu
mou
r ty
pe
Aut
hors
’ con
clus
ions
A
sing
le c
ours
e of
ver
tepo
rfin
PDT
sho
wed
tre
atm
ent
bene
fit
for
patie
nts
with
mul
tiple
non
-m
elan
oma
skin
can
cers
Bri
ef s
tudy
app
rais
al N
o cl
inic
ally
rel
evan
t co
mpa
rato
r tr
eatm
ent
was
use
d, t
here
w
as a
lack
of i
nfor
mat
ion
on
issu
es s
uch
as b
lindi
ng a
nd
allo
catio
n co
ncea
lmen
t, an
d th
e au
thor
s di
d no
t pr
esen
t m
any
resu
lts a
nd p
opul
atio
n de
tails
by
dia
gnos
is. I
t is
the
refo
re
diffi
cult
to m
ake
any
relia
ble
conc
lusi
ons
abou
t th
e ef
ficac
y of
ver
tepo
rfin
in p
atie
nts
with
BC
C
Appendix 15
232
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
233Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Mos
terd
et
al. (
2008
)86
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry T
he
Net
herl
ands
Lang
uage
Eng
lish
Stud
y de
sign
RC
T
(bet
wee
n-pa
rtic
ipan
t co
mpa
riso
n)N
o. o
f par
tici
pant
sTo
tal:
149
(173
lesi
ons
rand
omis
ed, 1
71
trea
ted)
Inte
rven
tion:
85
lesi
ons
Com
para
tor:
88 le
sion
sN
o. o
f rec
ruit
ing
cent
res
One
Follo
w-u
p pe
riod
an
d fr
eque
ncy
1–2
wk
for
surg
ery,
then
3, 6
, 12
and
18
mth
; 2, 3
, 4 a
nd 5
yr
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y nB
CC
Mai
n el
igib
ility
cri
teri
a Pr
evio
usly
unt
reat
ed p
rim
ary
nBC
C w
ith m
axim
um
diam
eter
of 2
0 m
m in
pa
tient
s of
18
yr o
r ol
der.
Preg
nanc
y, lif
e ex
pect
ancy
of
less
tha
n 5
yr a
nd u
se
of p
hoto
sens
itive
dru
gs
wer
e ex
clus
ion
crite
ria.
Tum
ours
wer
e ex
clud
ed
if re
curr
ent,
pigm
ente
d or
lo
cate
d on
hai
ry o
r co
ncav
e ar
eas.
Furt
her
deta
ils w
ere
repo
rted
Pati
ent
char
acte
rist
ics
% M
ale:
50M
ean
age:
65 yr
Mos
t tu
mou
rs w
ere
loca
ted
on t
he fo
rehe
ad/t
empl
e, b
ack
or n
ose
area
. Max
imum
mea
n tu
mou
r di
amet
er 9
.1 m
mC
onco
mit
ant
trea
tmen
t N
ot s
tate
d
Tria
l tre
atm
ents
ALA
–PD
T v
s Su
rgic
al e
xcis
ion
Inte
rven
tion
ALA
–PD
T: P
artia
l tum
our
debu
lkin
g pe
rfor
med
und
er lo
cal a
naes
thet
ic 3
wk
prio
r to
PD
T
trea
tmen
t. 20
% A
LA c
ream
app
lied
to le
sion
incl
udin
g 5-
mm
sur
roun
ding
are
a an
d co
vere
d w
ith o
cclu
sive
dr
essi
ng fo
r 4
hr. L
esio
n th
en il
lum
inat
ed u
sing
a
broa
dban
d m
etal
-hal
ogen
ligh
t so
urce
for
15 m
in w
ith
inte
nsity
of 1
00 m
Wcm
2 and
dos
e of
75
J/cm
2 . Are
a w
as t
hen
cove
red
and
re-il
lum
inat
ed a
fter
60 m
in. T
his
prod
uced
a fr
actio
nate
d tr
eatm
ent
on t
he s
ame
day
with
a t
otal
ligh
t do
se o
f 150
J/cm
2 . A
ny in
com
plet
e re
spon
ses
or r
ecur
rent
tum
ours
wer
e re
-tre
ated
su
rgic
ally
Com
para
tor
Surg
ical
Exc
isio
n: L
ocal
ana
esth
etic
usi
ng
lidoc
aine
(1%
) w
ith a
dren
alin
e fo
llow
ed b
y ex
cisi
on o
f th
e tu
mou
r an
d a
3-m
m s
urro
undi
ng m
argi
n. C
losu
re
was
by
sutu
res
or t
rans
posi
tion/
tran
spla
ntat
ion
depe
ndin
g on
lesi
on lo
catio
n. S
ectio
ns o
f the
late
ral
and
deep
mar
gins
wer
e hi
stol
ogic
ally
exa
min
ed; i
f re
sidu
al t
umou
r w
as fo
und
then
thi
s w
as r
egar
ded
as
a tr
eatm
ent
failu
re a
nd r
e-ex
cisi
ons
wer
e pe
rfor
med
un
til m
argi
ns w
ere
free
from
tum
our
Mor
bidi
ty 3
mth
: 78
/83
(94%
) C
R in
PD
T
and
86/8
8 (9
8%)
in S
E pa
tient
s, p
= 0.
27Fa
ilure
rat
es: C
umul
ativ
e in
cide
nce
of fa
ilure
pr
obab
ility
at
3 yr
was
2.
3% fo
r SE
and
30.
3%
for
PDT
(p
< 0.
001)
QoL
and
ret
urn
to
norm
al a
ctiv
ity
Not
as
sess
edA
Es
No
seri
ous
com
plic
atio
ns w
ere
obse
rved
Aut
hors
’ con
clus
ions
Tre
atm
ent
of n
BCC
with
SE
is s
igni
fican
tly m
ore
effe
ctiv
e th
an t
reat
men
t w
ith A
LA–
PDT
afte
r de
bulk
ing.
PDT
sho
uld
not
ther
efor
e be
use
d as
a s
tand
ard
trea
tmen
t fo
r nB
CC
Bri
ef s
tudy
app
rais
al T
his
was
a
wel
l-con
duct
ed a
nd g
ener
ally
w
ell-r
epor
ted
stud
y, w
hich
dra
ws
appr
opri
ate
conc
lusi
ons
and
can
be
cons
ider
ed t
o be
rel
iabl
e. A
s th
e au
thor
s su
gges
t fu
rthe
r st
udie
s ar
e re
quire
d to
exp
lore
pos
sibl
e va
riat
ions
in
PD
T t
reat
men
t
Appendix 15
232
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
233Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Rho
des
et a
l. (2
007)
85
Link
ed
publ
icat
ions
192–
197
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ries
Not
sta
ted
‘Eur
opea
n ho
spita
ls’
Lang
uage
Eng
lish
Stud
y de
sign
RC
T
(bet
wee
n-pa
rtic
ipan
t co
mpa
riso
n)N
o. o
f par
tici
pant
sTo
tal:
103
rand
omis
ed
(101
tre
ated
)In
terv
entio
n: 5
3 (6
0 le
sion
s)C
ompa
rato
r: 50
(58
le
sion
s)N
o. o
f rec
ruit
ing
cent
res
13Fo
llow
-up
peri
od
and
freq
uenc
y 3
mth
, th
en a
t 1,
2, 3
, 4 a
nd
5 yr
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y Pr
imar
y nB
CC
Mai
n el
igib
ility
cri
teri
a H
isto
logi
cally
con
firm
ed
nBC
C, p
revi
ously
un
trea
ted
in p
atie
nts
≥ 18
yr. P
atie
nts
with
mor
e th
an 1
0 le
sion
s, po
rphy
ria,
or G
orlin
syn
drom
e w
ere
excl
uded
. Fur
ther
ex
clus
ion
crite
ria
wer
e re
port
edPa
tien
t ch
arac
teri
stic
s%
Mal
e: 60
Age
ran
ge: 3
8–95
yrM
ean
age:
69 yr
(PD
T
grou
p), 6
7 yr
(su
rger
y gr
oup)
Aro
und
90%
of p
atie
nts
had
only
one
lesi
on, a
nd
arou
nd t
hree
-qua
rter
s of
le
sion
s w
ere
betw
een
5 an
d 14
mm
in d
iam
eter
. T
he m
ajor
ity o
f pat
ient
s w
ere
clas
sifie
d as
Fi
tzpa
tric
k sk
in t
ype
II or
III
, and
lesi
ons
wer
e m
ostly
on
the
face
/sca
lp/t
runk
an
d ne
ck
Tria
l tre
atm
ents
MA
L–PD
T v
s ex
cisi
on s
urge
ryIn
terv
enti
on S
urfa
ce s
cale
re
mov
ed u
sing
sca
lpel
or
cure
tte
(with
out a
naes
thes
ia).
The
n on
e or
tw
o PD
T c
ycle
s w
ith m
ethy
l am
inol
evul
inat
e (1
60 m
g/g)
, eac
h co
mpr
isin
g of
tw
o se
ssio
ns (
1 w
k ap
art)
. Cre
am w
as a
pplie
d 1
mm
thi
ck a
nd t
o 5
mm
of
sur
roun
ding
tis
sue,
the
n co
vere
d w
ith a
n oc
clus
ive
dres
sing
for
3 hr
. Cre
am
then
was
hed
off w
ith 0
.9%
sa
line
solu
tion
imm
edia
tely
be
fore
illu
min
atio
n w
ith
non-
cohe
rent
red
ligh
t (5
70–6
70 n
m, t
otal
flue
nce
75 J/
cm2 ,
fluen
ce r
ate
of 5
0 to
200
mW
/cm
2 ), m
ean
light
de
nsity
of 1
27 m
W/c
m2 f
rom
a
stan
dard
ligh
t so
urce
If no
t C
R b
y 3m
th, 2
nd
trea
tmen
t cy
cle
adm
inis
tere
d.
76%
of l
esio
ns t
reat
ed w
ith
one
cycl
e on
lyC
ompa
rato
r Si
mpl
e el
liptic
al e
xcis
ion
surg
ery
with
at
leas
t 5-
mm
mar
gins
. Lo
cal a
naes
thes
ia
Mor
talit
y Fo
ur p
atie
nts
in e
ach
grou
p di
ed d
urin
g FU
(al
l co
nsid
ered
to
be u
nrel
ated
to
trea
tmen
t)M
orbi
dity
At
3 m
th: 4
8 le
sion
s (9
1%, 5
0 pa
tient
s) in
the
PD
T
grou
p, an
d 51
lesi
ons
(98%
, 47
patie
nts)
in t
he s
urge
ry g
roup
, sh
owed
CR
, mea
n di
ff =
4.8%
, ns.
At
1 yr
: 44/
53 P
DT
lesi
ons
(83%
) ha
d C
R v
s 50
/52
(96%
) su
rger
y le
sion
s (p
= 0
.15)
. Rec
urre
nce
was
4%
in P
DT
gro
up v
s 0%
in s
urge
ry g
roup
. At
2 yr
: 32/
53 (
60%
) PD
T
lesi
ons
had
CR
vs
44/5
2 (8
5%)
surg
ery
lesi
ons.
By t
his
stag
e, 1
1 (2
1%)
of P
DT
lesi
ons
wer
e lo
st t
o FU
vs
six
(11%
) su
rger
y le
sion
s. R
ecur
renc
e w
as 9
% in
PD
T g
roup
vs
2% in
sur
gery
gro
up. A
t 36
mth
: CR
79%
in P
DT
gro
up v
s 96
% in
sur
gery
gro
up. R
ecur
renc
e w
as 1
0% in
PD
T g
roup
vs
2% in
sur
gery
gro
up. A
t 5
yr: C
R w
as
76%
in t
he P
DT
gro
up a
nd 9
6% in
the
sur
gery
gro
up (
per-
prot
ocol
po
pula
tion,
p =
0.0
1). T
here
was
rec
urre
nce
in 1
4% o
f les
ions
in
PDT
gro
up a
nd 4
% in
the
sur
gery
gro
up (
p =
0.09
). O
nly
one
lesi
on
(in t
he s
urge
ry g
roup
) re
curr
ed w
ithin
the
3-
to 5
-yr
FU p
erio
d.
In t
he P
DT
gro
up, t
here
was
no
evid
ence
tha
t th
e re
curr
ence
rat
e w
as h
ighe
r in
larg
er le
sion
sQ
oL a
nd r
etur
n to
nor
mal
act
ivit
y C
osm
etic
out
com
e w
as
rate
d by
inve
stig
ator
as
bein
g: A
t 3m
th, e
xcel
lent
or
good
in
36/4
4 pa
tient
s (8
2%)
havi
ng P
DT
vs
15/4
5 pa
tient
s (3
3%)
havi
ng
surg
ery
(p <
0.0
01).
At
1 yr
, exc
elle
nt o
r go
od in
33
of 4
2 (7
9%)
PDT
pat
ient
s vs
17
of 4
5 (3
8%)
surg
ery
patie
nts
(p <
0.0
01).
At
2 yr
, ex
celle
nt o
r go
od in
24/
29 (
83%
) PD
T p
atie
nts
vs 1
6 of
39
(41%
) su
rger
y pa
tient
s (p
< 0
.001
). A
t 36
mth
, exc
elle
nt o
r go
od in
83%
of
PD
T p
atie
nts
vs 3
7% s
urge
ry p
atie
nts.
At
5yr,
exce
llent
or
good
in
27
of 3
1 (8
7%)
PDT
pat
ient
s vs
19
of 3
5 (5
4%)
surg
ery
patie
nts,
p =
0.00
7). P
atie
nts
also
rat
ed g
loba
l cos
met
ic o
utco
me
on a
4-
poin
t sc
ale
at 3
, 12
and
24 m
th. N
o si
gnifi
cant
diff
eren
ce a
t 3
mth
, at
12
mth
exc
elle
nt o
r go
od in
41/
42 (
98%
) fo
r PD
T p
atie
nts
vs
36/4
3 (8
4%)
for
surg
ery,
p =
0.03
. At
24 m
th, P
DT
pat
ient
s re
port
ed
28/2
9 (9
7%)
vs 2
7/36
(75
%)
for
surg
ery,
p =
0.04
AE
s M
ore
PDT
pat
ient
s re
port
ed A
Es [
27/5
2 (5
2%)
vs 1
4/49
(29%
), p
= 0.
03].
Mos
t AEs
wer
e tr
ansi
ent
loca
l rea
ctio
ns s
uch
as b
urni
ng
sens
atio
ns, s
kin
pain
, or
eryt
hem
a. O
ne P
DT
pat
ient
had
to
stop
tre
atm
ent
due
to a
sev
ere
burn
ing
sens
atio
n; t
hree
sur
gery
pa
tient
s ha
d sk
in in
fect
ions
Aut
hors
’ con
clus
ions
Lo
ng-t
erm
FU
indi
cate
s su
peri
or e
ffica
cy o
f su
rger
y to
PD
T. H
owev
er,
PDT
is a
lso
an e
ffect
ive
trea
tmen
t an
d ex
hibi
ts a
m
ore
favo
urab
le c
osm
etic
ou
tcom
eB
rief
stu
dy a
ppra
isal
T
his
gene
rally
wel
l-co
nduc
ted
tria
l, w
hich
ha
d a
long
FU
per
iod,
was
re
port
ed in
tw
o pa
pers
an
d fo
ur a
bstr
acts
. The
re
sults
are
like
ly t
o be
re
liabl
e, a
lthou
gh t
he
3-m
th C
R r
esul
ts d
id v
ary
slig
htly
bet
wee
n re
port
s
Appendix 15
234
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
235Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Sch
leie
r et
al.
(200
7)81
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry G
erm
any
Lang
uage
Eng
lish
Stud
y de
sign
RC
T
(bet
wee
n-pa
rtic
ipan
t co
mpa
riso
n)N
o. o
f par
tici
pant
sTo
tal:
24 (
112
lesi
ons)
Inte
rven
tion:
13
Com
para
tor:
11N
o. o
f rec
ruit
ing
cent
res
One
Follo
w-u
p pe
riod
an
d fr
eque
ncy
2, 4
an
d 12
wk
and
6 m
th
afte
r pr
imar
y tr
eatm
ent
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y Su
perfi
cial
BC
CM
ain
elig
ibili
ty
crit
eria
His
tolo
gica
lly
veri
fied
BCC
of t
he s
kin,
hi
stol
ogic
ally
pro
ven
supe
rfici
al B
CC
with
no
dee
p in
filtr
atio
n (<
2 m
m),
no m
orph
eic
and
pigm
ente
d BC
C a
nd
good
pat
ient
com
plia
nce.
Ex
clus
ion
crite
ria
wer
e: U
ncle
ar h
isto
logy
, cl
inic
ally
nBC
C, e
xpec
ted
poor
com
plia
nce
of
the
patie
nt, u
ntre
ated
di
abet
es m
ellit
us a
nd
preg
nanc
yPa
tien
t ch
arac
teri
stic
s%
Mal
e: 54
Age
ran
ge: 4
2–96
yrM
ean
age
74 yr
The
vas
t m
ajor
ity o
f the
tu
mou
rs w
ere
loca
ted
in
the
head
and
nec
k ar
ea.
The
ave
rage
dia
met
er
of t
he le
sion
s w
as 7
mm
(r
ange
3–1
2 m
m). T
hree
pa
tient
s w
ith G
GS
wer
e in
clud
ed in
the
stu
dyC
onco
mit
ant
trea
tmen
t N
ot s
tate
d
Tria
l tre
atm
ents
ALA
-bas
ed P
DT
vs
mA
LA-b
ased
PD
TIn
terv
enti
on A
LA a
nd m
ALA
gel
s w
ere
prep
ared
less
tha
n 1h
r be
fore
tr
eatm
ent
by d
isso
lvin
g in
a c
old
(app
rox
4°C
) th
erm
o ge
l (Lu
trol
F-1
27)
up t
o a
conc
entr
atio
n of
10%
of A
LA (
mA
LA)/
ml
(w/v
). The
gel
was
app
lied
3 m
m b
eyon
d th
e vi
sibl
e m
argi
n of
the
tum
our
and
was
ap
prox
imat
ely
5 m
m t
hick
. The
are
a w
as
cove
red
with
pla
ster
and
pro
tect
ed fr
om
light
. 3 h
r la
ter,
resi
dues
wer
e re
mov
ed
and
tum
our
area
s ci
rcle
d w
ith a
blu
e sk
in
mar
ker. T
he le
sion
was
the
n ill
umin
ated
w
ith a
dio
de la
ser
equi
pped
with
a
mic
role
ns fi
bre.
The
pow
er d
ensi
ty w
as
0.1 W
/cm
2 and
the
ene
rgy
dens
ity w
as
120
J/cm
2 . A d
iam
eter
of t
he ir
radi
ated
ar
ea o
f app
roxi
mat
ely
10 m
m w
as
sele
cted
and
dis
tanc
e la
ser-
diffu
ser-
skin
co
rres
pond
ed t
o 15
mm
. The
pro
cedu
re
was
per
form
ed w
ith o
r w
ithou
t lo
cal
anae
sthe
sia
acco
rdin
g to
the
pai
n m
anag
emen
t ne
eds
of t
he p
atie
nt. I
n ca
ses
whe
re t
reat
men
t w
as o
nly
part
ially
su
cces
sful
, the
the
rapy
was
rep
eate
d af
ter
the
final
exa
min
atio
n (1
2th
wk)
. Fu
rthe
r PD
T p
aram
eter
s w
ere
not
repo
rted
Com
para
tor
See
‘Inte
rven
tion’
for
deta
ils
Mor
bidi
ty A
LA g
roup
: 44
of 7
2 BC
C
(61%
) sh
owed
a C
R 1
2 w
k af
ter
the
1st
trea
tmen
t vs
mA
LA g
roup
: 23
of 4
0 BC
C
(58%
) N
ST
here
was
no
stat
istic
ally
sig
nific
ant
diffe
renc
e in
par
tial s
ucce
sses
(re
duct
ion
of t
he d
iam
eter
of t
he B
CC
of a
t le
ast
50%
of t
he in
itial
tum
our
size
) be
twee
n th
e gr
oups
. Thr
ee t
umou
rs (
4%)
in t
he
ALA
gro
up a
nd o
ne B
CC
(3%
) di
d no
t re
spon
d to
tre
atm
ent
and
show
ed n
o re
duct
ion
in t
umou
r si
ze. T
hese
pat
ient
s w
ere
give
n su
rgic
al t
reat
men
t. Ei
ght
BCC
s in
the
ALA
gro
up a
nd fi
ve in
the
m
ALA
gro
up d
evel
oped
a r
ecur
renc
e du
ring
the
6-m
th p
erio
d. A
fter
a se
cond
PD
T, se
ven
lesi
ons
in t
he A
LA g
roup
and
se
ven
in t
he m
ALA
gro
up w
ere
trea
ted
succ
essf
ully
QoL
and
ret
urn
to n
orm
al a
ctiv
ity
Not
ass
esse
dA
Es
Dur
ing
illum
inat
ion,
eig
ht A
LA
patie
nts
and
five
mA
LA p
atie
nts
expe
rien
ced
mod
erat
ely
pain
ful
sens
atio
ns in
the
tre
ated
are
(1–
4 on
the
pa
in s
cale
). Tw
o pa
tient
s in
the
mA
LA
grou
p ha
d st
abbi
ng p
ain
sens
atio
ns
(leve
l 6–7
on
the
pain
sca
le)
duri
ng t
he
lase
r ap
plic
atio
n an
d ha
d to
be
trea
ted
with
loca
l ana
esth
etic
. Fiv
e pa
tient
s in
A
LA g
roup
and
tw
o in
mA
LA g
roup
felt
mod
erat
e pa
in s
ensa
tions
up
to t
he 3
rd
day
post
illu
min
atio
n (1
–3 o
n th
e pa
in
scal
e)
Aut
hors
’ con
clus
ions
The
the
rape
utic
ou
tcom
e of
thi
s pi
lot
stud
y sh
owed
no
diff
eren
ce b
etw
een
PDT
with
ALA
an
d m
ALA
. Thi
s pr
elim
inar
y re
sult
will
re
quire
con
firm
atio
n in
furt
her
rese
arch
Bri
ef s
tudy
app
rais
al T
his
was
a p
ilot
stud
y in
pre
para
tion
for
a la
rger
clin
ical
tr
ial. A
s su
ch, i
t is
like
ly t
o ha
ve b
een
unde
rpow
ered
to
dete
ct s
tatis
tical
ly
sign
ifica
nt d
iffer
ence
s fo
r at
leas
t so
me
of t
he o
utco
mes
inve
stig
ated
. Tre
atm
ent
met
hods
wer
e w
ell d
escr
ibed
but
st
udy
met
hods
, suc
h as
met
hods
of
rand
omis
atio
n, c
once
alm
ent
of a
lloca
tion
and
blin
ding
, wer
e no
t re
port
ed in
det
ail
GG
S, G
orlin
–Gol
tz s
yndr
ome.
Appendix 15
234
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
235Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Sol
er e
t al.
(200
0)82
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry N
orw
ayLa
ngua
ge E
nglis
hSt
udy
desi
gn
RC
T (
betw
een-
part
icip
ant
com
pari
son)
No.
of
part
icip
ants
Tota
l: 83
(24
5 le
sion
s)In
terv
entio
n: 4
1 (1
11 le
sion
s)C
ompa
rato
r: 42
(1
34 le
sion
s)N
o. o
f rec
ruit
ing
cent
res
One
Fo
llow
-up
peri
od
and
freq
uenc
y FU
at
1 w
k, an
d 3
and
6 m
th. S
ome
part
icip
ants
als
o fo
llow
ed u
p af
ter
1 an
d 2
yr
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y Su
perfi
cial
BC
CM
ain
elig
ibili
ty c
rite
ria
Patie
nts
with
his
tolo
gica
lly/
cyto
logi
cally
con
firm
ed
supe
rfici
al B
CC
with
th
ickn
ess
< 1
mm
, and
di
amet
er <
3 cm
. Pat
ient
s w
ith
few
er t
han
six
lesi
ons
Pati
ent
char
acte
rist
ics
% M
ale:
47
Mea
n ag
e: 62
yrA
ll C
auca
sian
Con
com
itan
t tr
eatm
ent
Not
sta
ted
Tria
l tre
atm
ents
PD
T-la
ser
vs P
DT-
broa
dban
d la
mp
Inte
rven
tion
PD
T-la
ser:
Pre-
trea
tmen
t w
ith d
ress
ing
soak
ed w
ith 9
9%
dim
ethy
lsul
phox
ide
for
15 m
in fo
llow
ed
by 2
0% A
LA c
ream
and
cov
erin
g w
ith
occl
usiv
e dr
essi
ng fo
r 3h
. Cre
am w
as
was
hed
off b
efor
e ex
posu
re t
o lig
ht
of 6
30 n
m fr
om a
cop
per
vapo
ur la
ser
pum
ping
a d
ye la
ser.
Irra
dian
ce o
f 12
0–15
0 m
W/c
m2 ,
and
a lig
ht d
ose
of
100–
150
J/cm
2 (m
edia
n do
se 1
00 J/
cm2 )
Com
para
tor
PDT-
broa
dban
d la
mp:
As
for
PDT-
lase
r ex
cept
ligh
t so
urce
was
a
150W
hal
ogen
bul
b br
oadb
and
lam
p, gi
ving
filte
red
light
of b
etw
een
570
and
740n
m. I
rrad
ianc
e w
as 1
00–1
80 m
W/c
m2
and
tota
l lig
ht d
ose
rang
ed fr
om 1
50–
200
J/cm
2 with
med
ian
light
dos
e of
20
0 J/c
m2 . T
otal
irra
dian
ce in
clud
ing
infr
a-re
d w
as 1
35–2
40 m
W/c
m2
Mor
bidi
ty O
vera
ll, th
ere
wer
e no
st
atis
tical
ly s
igni
fican
t di
ffere
nces
(p
= 0
.49)
in r
espo
nse
rate
s (c
ompl
ete,
pa
rtia
l, or
non
e) b
etw
een
the
grou
ps
[CR
was
95/
111
lesi
ons
(86%
) fo
r la
ser
vs 1
10/1
34 (
82%
) fo
r la
mp]
. Pat
ient
s w
ith C
R w
ere
follo
wed
up
beyo
nd
the
prot
ocol
6-m
th p
erio
d. D
ata
wer
e pr
esen
ted,
but
not
sta
tistic
ally
ana
lyse
d –
recu
rren
ce a
fter
2 yr
s oc
curr
ed in
fo
ur le
sion
s fo
r th
e la
ser
grou
p, an
d fiv
e le
sion
s fo
r th
e la
mp
grou
pQ
oL a
nd r
etur
n to
nor
mal
act
ivit
y O
vera
ll th
ere
wer
e no
sta
tistic
ally
si
gnifi
cant
diff
eren
ces
in c
osm
etic
res
ults
(p
= 0
.075
). R
esul
ts w
ere
scor
ed a
s be
ing
exce
llent
or
good
in 8
0 le
sion
s (8
4%)
in
the
lase
r gr
oup
vs 1
02 le
sion
s (9
2%)
in
the
lam
p gr
oup
AE
s D
urin
g th
e 1s
t w
k af
ter
trea
tmen
t 68
% o
f the
lase
r gr
oup
and
74%
of t
he
lam
p gr
oup
patie
nts
repo
rted
som
e de
gree
of d
isco
mfo
rt (
e.g.
stin
ging
, itc
hing
, pai
n). T
here
wer
e no
sta
tistic
ally
si
gnifi
cant
diff
eren
ces
betw
een
the
grou
ps fo
r AEs
eith
er d
urin
g or
afte
r tr
eatm
ent.
No
SAEs
wer
e re
port
ed
duri
ng 6
-mth
FU
per
iod
Aut
hors
’ con
clus
ions
Top
ical
ALA
–PD
T w
ith a
bro
adba
nd h
alog
en li
ght
sour
ce g
ives
cur
e ra
tes
and
cosm
etic
ou
tcom
e si
mila
r to
tho
se o
btai
ned
with
a
lase
r so
urce
Bri
ef s
tudy
app
rais
al A
lthou
gh t
his
was
qui
te a
wel
l-con
duct
ed s
tudy
, the
re
wer
e st
ill is
sues
whi
ch q
uest
ion
the
relia
bilit
y of
its
resu
lts: t
he a
utho
rs
ackn
owle
dged
tha
t th
e op
timum
w
avel
engt
h fo
r ALA
–PD
T is
635
nm
, but
63
0 nm
was
use
d fo
r th
e la
ser
grou
p, fo
r re
ason
s of
pra
ctic
ality
; lig
ht d
oses
var
ied
betw
een
patie
nts
with
in a
tre
atm
ent
grou
p; a
nd t
he M
/F r
atio
diff
ered
su
bsta
ntia
lly b
etw
een
the
trea
tmen
t gr
oups
Appendix 15
236
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
237Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Sze
imie
s et
al. (
2008
)80
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ries
A
ustr
alia
, Ger
man
y, Sw
itzer
land
, UK
Lang
uage
Eng
lish
Stud
y de
sign
R
CT
(be
twee
n-pa
rtic
ipan
t co
mpa
riso
n)N
o. o
f pa
rtic
ipan
tsTo
tal:
196
(182
an
alys
ed)
Inte
rven
tion:
100
Com
para
tor:
96N
o. o
f rec
ruit
ing
cent
res
27: 1
0 in
U
K, 1
0 in
Ger
man
y, tw
o in
Sw
itzer
land
, fiv
e in
Aus
tral
iaFo
llow
-up
peri
od
and
freq
uenc
y 3,
6
and
12 m
th
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y Su
perfi
cial
BC
CM
ain
elig
ibili
ty c
rite
ria
Patie
nts
over
18
yr w
ith
hist
olog
ical
ly c
onfir
med
pr
imar
y sB
CC
sui
tabl
e fo
r si
mpl
e ex
cisi
on s
urge
ry.
Patie
nts
with
mor
e th
an fi
ve
lesi
ons,
lesi
ons
in t
he m
id-
face
are
a, le
sion
s sm
alle
r th
an 8
mm
or
larg
er t
han
20 m
m w
ere
excl
uded
(o
ther
cri
teri
a re
port
ed)
Pati
ent
char
acte
rist
ics
% M
ale:
67A
ge r
ange
: 31–
92 yr
Mea
n ag
e: 64
yrA
ll pa
tient
s w
ere
Cau
casi
an,
and
the
mea
n no
. of l
esio
ns
per
patie
nt w
as 1
.4 (
rang
e 1–
5). M
ost
lesi
ons
wer
e lo
cate
d on
the
tru
nk o
r ne
ckC
onco
mit
ant
trea
tmen
t co
ncur
rent
tre
atm
ent
on
the
lesi
on a
reas
was
not
pe
rmitt
ed
Tria
l tre
atm
ents
MA
L–PD
T v
s Su
rger
yIn
terv
enti
on M
AL–
PDT:
Pat
ient
s re
ceiv
ed t
wo
trea
tmen
t se
ssio
ns, 7
d
apar
t. Le
sion
s w
ere
prep
ared
pri
or t
o ea
ch s
essi
on if
dee
med
nec
essa
ry b
y re
mov
ing
crus
ts a
nd r
ough
enin
g th
e su
rfac
e. 1
60 m
g/g
of M
AL
crea
m w
as
appl
ied
1 m
m t
hick
to
the
lesi
on a
nd
surr
ound
5–1
0 m
m o
f ski
n an
d co
vere
d w
ith a
n oc
clus
ive
dres
sing
for
3 hr
. Cre
am
was
was
hed
off u
sing
sal
ine
solu
tion
and
the
area
exp
osed
to
red
light
from
a
larg
e-fie
ld L
ED s
ourc
e fo
r be
twee
n 7
and
10 m
in, t
otal
ligh
t do
se 3
7 J/c
m2 .
Min
i-des
k fa
ns w
ere
prov
ided
to
cool
the
ir
radi
atio
n si
tes
duri
ng li
ght
expo
sure
Com
para
tor
Surg
ery:
One
sim
ple
ellip
tical
exc
isio
n su
rger
y w
as p
erfo
rmed
ac
cord
ing
to t
he in
vest
igat
ors
rout
ine
prac
tice
with
an
estim
ated
3-m
m m
argi
n fr
om e
stim
ated
edg
e of
the
lesi
on
Mor
bidi
ty (
all p
er p
roto
col a
naly
ses)
3-m
th c
ompl
ete
lesi
on r
espo
nse:
118/
128
(92%
) fo
r PD
T v
s 11
7/11
8 (9
9%)
in
surg
ery
12-m
th le
sion
rec
urre
nce:
11/1
18 (
9%)
for
PDT
vs
0.11
7 (0
%)
for
surg
ery
QoL
and
ret
urn
to n
orm
al a
ctiv
ity
Cos
met
ic o
utco
me
asse
ssed
by
patie
nt
and
inve
stig
ator
, in
both
cas
es P
DT
tr
eatm
ent
was
judg
ed t
o be
sup
erio
r12
-mth
inve
stig
ator
rat
ed a
sses
smen
t: 77
/83
(93%
) for
PD
T a
nd 4
4/86
(51%
) for
su
rger
y w
ere
cons
ider
ed a
s a
‘suc
cess
’, p
< 0.
001
AE
s Tre
atm
ent-
rela
ted
AE
wer
e hi
gher
in
the
PD
T (
37%
) th
an s
urge
ry (
15%
) gr
oup.
Mos
t re
late
d A
Es w
ere
of m
ild
to m
oder
ate
seve
rity
and
wer
e m
ost
com
mon
ly p
hoto
sens
itivi
ty (
31%
) re
actio
n fo
r PD
T a
nd w
ound
infe
ctio
n (5
%)
for
surg
ery
patie
nts
11%
of P
DT
pat
ient
s w
ith r
elat
ed
AEs
req
uire
d tr
eatm
ent
whi
le 5
7% o
f su
rger
y pa
tient
s w
ith r
elat
ed A
Es n
eede
d tr
eatm
ent
No
SAEs
wer
e re
cord
ed t
hat
wer
e co
nsid
ered
to
be r
elat
ed t
o ei
ther
tr
eatm
ent
Aut
hors
’ con
clus
ions
MA
L–PD
T
has
high
leve
ls o
f effi
cacy
and
exc
elle
nt
cosm
etic
out
com
es w
hen
trea
ting
sBC
C a
nd s
houl
d be
con
side
red
as a
n al
tern
ativ
e to
sur
gery
Bri
ef s
tudy
app
rais
al T
his
was
a w
ell-
repo
rted
and
con
duct
ed t
rial
; how
ever
, lo
nger
-ter
m F
U w
ould
pro
vide
use
ful
outc
ome
data
on
the
recu
rren
ce r
ates
. It
was
not
cle
ar if
the
stu
dy w
as a
dequ
atel
y po
wer
ed t
o sh
ow e
quiv
alen
ce o
f tr
eatm
ents
. Giv
en t
hat
incl
uded
pat
ient
s w
ere
rest
rict
ed t
o th
ose
elig
ible
for
surg
ery,
as t
he a
utho
rs h
ave
high
light
ed it
se
ems
plau
sibl
e th
at P
DT
may
be
mor
e ef
fect
ive
than
sho
wn
here
Appendix 15
236
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
237Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Top
e et
al.
(200
4)78
Dat
a so
urce
Abs
trac
tC
ount
ry U
SALa
ngua
ge E
nglis
hSt
udy
desi
gn R
CT
(b
etw
een-
part
icip
ant
com
pari
son)
No.
of p
arti
cipa
nts
Tota
l: 65
(80
lesi
ons)
Inte
rven
tion:
33
patie
nts
(41
lesi
ons)
Com
para
tor:
32 p
atie
nts
(39
lesi
ons)
No.
of r
ecru
itin
g ce
ntre
s N
ot s
tate
d bu
t de
scri
bed
as b
eing
m
ultic
entr
eFo
llow
-up
peri
od a
nd
freq
uenc
y N
ot c
lear
, bu
t ap
pear
ed t
o be
at
leas
t 6
mth
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y nB
CC
Mai
n el
igib
ility
cri
teri
a N
ot s
tate
dPa
tien
t ch
arac
teri
stic
s N
ot s
tate
dC
onco
mit
ant
trea
tmen
t N
ot s
tate
d
Tria
l tre
atm
ents
MA
L–PD
T (
met
hyl
amin
olev
ulin
ate)
vs
PDT
(pl
aceb
o cr
eam
)In
terv
enti
on M
AL–
PDT:
Pat
ient
s re
ceiv
ed t
wo
cycl
es (
1 w
k ap
art)
of
met
hyl a
min
olev
ulin
ate
PDT.
The
re w
as
surf
ace
debr
idem
ent
and
slig
ht le
sion
de
bulk
ing
prio
r to
PD
T. BC
C w
ith
part
ial c
linic
al r
espo
nse
at 3
mth
wer
e re
-tre
ated
. Fur
ther
PD
T p
aram
eter
s w
ere
not
repo
rted
Com
para
tor A
s fo
r M
AL–
PDT
usi
ng
plac
ebo
crea
m
Mor
bidi
ty C
ompl
ete
clin
ical
res
pons
e w
as 8
0% (
33/4
1 le
sion
s) fo
r ac
tive
PDT
vs
51%
(20
/39
lesi
ons)
for
plac
ebo
PDT.
Com
plet
e hi
stol
ogic
al r
espo
nse
was
78%
(32
/41
lesi
ons)
vs
33%
(13
/39
lesi
ons)
, bot
h ap
pear
ed t
o be
at
p <
0.00
1Q
oL a
nd r
etur
n to
nor
mal
act
ivit
y Fo
r si
tes
show
ing
com
plet
e cl
inic
al
resp
onse
, inve
stig
ator
-ass
esse
d co
smet
ic
outc
ome
was
exc
elle
nt o
r go
od in
93%
of
act
ive
PDT
vs
90%
of p
lace
bo P
DT
Patie
nt s
atis
fact
ion
with
PD
T c
ompa
red
with
pre
viou
s tr
eatm
ent
was
bet
ter
in
60%
of M
AL–
PDT
pat
ient
s, an
d 52
% in
pl
aceb
o PD
T p
atie
nts
AE
s The
re w
ere
no s
yste
mic
AEs
in
eith
er g
roup
. Loc
al A
Es: 9
1% in
the
ac
tive
grou
p vs
75%
in t
he p
lace
bo
grou
p. M
ild t
o m
oder
ate
eryt
hem
a, bu
rnin
g, st
ingi
ng, a
nd p
ain
foun
d in
bot
h gr
oups
. Pai
n oc
curr
ed fo
r a
med
ian
of 2
d in
act
ive
PDT
gro
up v
s 3–
6 d
in
plac
ebo
PDT
gro
up. A
ll SA
Es in
bot
h gr
oups
wer
e no
t re
late
d to
tre
atm
ent
Aut
hors
’ con
clus
ions
PD
T w
as
clin
ical
ly a
nd h
isto
logi
cally
sup
erio
r to
pl
aceb
o PD
T in
tre
atin
g nB
CC
Bri
ef s
tudy
app
rais
al V
ery
little
in
form
atio
n w
as a
vaila
ble
in t
his
abst
ract
. It
was
not
alw
ays
clea
r w
heth
er r
esul
ts w
ere
for
lesi
ons
or
indi
vidu
al p
atie
nts
Appendix 15
238
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
239Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Wan
g et
al.
(200
1)88
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry S
wed
enLa
ngua
ge E
nglis
hSt
udy
desi
gn R
CT
(b
etw
een-
part
icip
ant
com
pari
son)
No.
of p
arti
cipa
nts
Tota
l: 88
Inte
rven
tion:
47
Com
para
tor:
41N
o. o
f rec
ruit
ing
cent
res
One
Follo
w-u
p pe
riod
an
d fr
eque
ncy
FU
at 1
, 4, 8
and
12
wk,
and
at 1
yr
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y N
on-m
orph
oeic
BC
Cs
(sup
erfic
ial a
nd
nodu
lar)
Mai
n el
igib
ility
cri
teri
a Pa
tient
s ag
ed 2
0–90
, with
hi
stop
atho
logi
cally
ver
ified
BC
Cs
suita
ble
for
both
PD
T a
nd c
ryos
urge
ry, w
ere
elig
ible
. Exc
lusi
on c
rite
ria
(e.g
. pre
gnan
cy)
wer
e al
so
repo
rted
Pati
ent
char
acte
rist
ics
% M
ale:
50A
ge r
ange
: 42–
88 yr
The
re w
ere
39 p
atie
nts
with
sup
erfic
ial B
CC
s an
d 49
with
nBC
Cs.
54%
wer
e on
the
tru
nk, 2
8% o
n he
ad
and
neck
, 11%
on
legs
, and
7%
on
arm
sC
onco
mit
ant
trea
tmen
t Lo
cal a
naes
thet
ic a
vaila
ble
duri
ng p
roce
dure
s. U
se
of a
nalg
esic
dru
gs w
as
perm
itted
for
pain
rel
ief
duri
ng t
he w
eek
follo
win
g pr
oced
ures
Tria
l tre
atm
ents
ALA
–PD
T v
s C
ryot
hera
pyIn
terv
enti
on L
esio
ns w
ere
1st
prep
ared
(re
mov
al o
f str
atum
cor
neum
m
ater
ial u
sing
sca
lpel
/96%
alc
ohol
/is
oton
ic s
alin
e). 2
0% A
LA w
as t
hen
appl
ied
to le
sion
with
1-c
m m
argi
n, a
nd
cove
red
with
a t
hin
occl
usiv
e dr
essi
ng.
6 hr
afte
r ALA
, 635
-nm
ligh
t th
roug
h a
600-µ
m o
ptic
al fi
bre
(with
a c
lear
-cut
po
lishe
d en
d) fr
om a
Nd:
YAG
lase
r w
as
appl
ied.
The
sin
gle
light
dos
e w
as 6
0 J/c
m2 ,
and
the
mea
n flu
ence
rat
e 80
mW
/cm
2 . La
rger
lesi
ons
had
to b
e ill
umin
ated
with
m
ore
than
one
ligh
t so
urce
. Pat
ient
s w
ith p
ain
duri
ng li
ght
expo
sure
rec
eive
d w
ater
spr
ay a
t 15
–20°
C. A
dditi
onal
tr
eatm
ent
give
n if
ther
e w
as e
vide
nce
of r
esid
ual t
umou
r gr
owth
at
the
4, 8
or
12 w
k ex
amin
atio
nsC
ompa
rato
r Tre
atm
ent
with
a li
quid
ni
trog
en u
nit
usin
g a
spra
y te
chni
que.
Two
free
ze–t
haw
cyc
les
wer
e gi
ven,
and
the
ar
ea fr
ozen
for
25–3
0 s
each
tim
e, w
ith
a th
awin
g pe
riod
of 2
–4 m
in in
bet
wee
n.
Add
ition
al t
reat
men
t gi
ven
if th
ere
was
ev
iden
ce o
f res
idua
l tum
our
grow
th a
t th
e 4-
, 8-
or 1
2-w
k ex
amin
atio
ns
Mor
talit
y O
ne p
atie
nt d
ied
in e
ach
grou
p af
ter
the
3-m
th F
U. B
oth
deat
hs
wer
e un
rela
ted
to B
CC
and
its
trea
tmen
tM
orbi
dity
Mor
e pa
rtic
ipan
ts in
the
PD
T
grou
p ha
d to
be
re-t
reat
ed (
13/4
4, 3
0%)
com
pare
d w
ith t
he c
ryos
urge
ry g
roup
(1
/39,
3%
). The
rec
urre
nce
rate
at
1 yr
w
as h
ighe
r in
the
PD
T g
roup
(11
/44,
25%
vs
6/3
9, 1
5%),
thou
gh n
ot s
tatis
tical
ly
sign
ifica
nt (
and
the
PDT
gro
up h
ad fe
wer
cl
inic
ally
obv
ious
rec
urre
nces
). A
fter
1 w
k, th
e PD
T g
roup
had
a s
igni
fican
tly
shor
ter
heal
ing
time
in t
erm
s of
le
akag
e an
d oe
dem
a (p
< 0
.001
), bu
t no
t er
ythe
ma.
The
re w
as a
lso
a si
gnifi
cant
di
ffere
nce
in le
akag
e at
1 m
th, f
avou
ring
th
e PD
T g
roup
QoL
and
ret
urn
to n
orm
al a
ctiv
ity
The
cos
met
ic o
utco
me
was
sig
nific
antly
be
tter
at
1 yr
in t
he P
DT
gro
up fo
r hy
popi
gmen
tatio
n, s
car
form
atio
n,
tissu
e de
fect
s (a
ll p
< 0.
001)
, and
hy
perp
igm
enta
tion
(p <
0.0
5)A
Es T
here
was
no
stat
istic
ally
si
gnifi
cant
diff
eren
ce in
mea
n pa
in
VAS
scor
es d
urin
g tr
eatm
ent
(PD
T
43 v
s cr
yosu
rger
y 32
). O
ne P
DT
pa
tient
req
uire
d lo
cal a
naes
thet
ic. O
ne
cryo
surg
ery
patie
nt d
evel
oped
a b
acte
rial
in
fect
ion
at t
he t
reat
men
t si
te. D
urin
g th
e 1s
t w
eek
post
tre
atm
ent
eigh
t PD
T
patie
nts
and
two
cryo
surg
ery
patie
nts
used
ana
lges
ic m
edic
atio
n (p
< 0
.05)
Aut
hors
’ con
clus
ions
ALA
–PD
T
is c
ompa
rabl
e w
ith c
ryos
urge
ry
as a
tre
atm
ent
mod
ality
for
BCC
s. R
etre
atm
ents
are
mor
e co
mm
on w
ith
PDT,
but
this
can
eas
ily b
e pe
rfor
med
du
e to
sho
rter
hea
ling
times
, les
s sc
arri
ng, a
nd b
ette
r co
smet
ic o
utco
me,
w
hich
follo
ws A
LA–P
DT
Bri
ef s
tudy
app
rais
al T
his
stud
y w
as
gene
rally
qui
te w
ell c
ondu
cted
and
the
re
sults
are
like
ly t
o be
rel
iabl
e. H
owev
er,
mor
e in
form
atio
n on
loss
es t
o FU
and
an
y sa
mpl
e si
ze c
alcu
latio
n us
ed, w
ould
ha
ve b
een
usef
ul
Appendix 15
238
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
239
Appendix 16 Barrett’s oesophagus data extraction
Appendix 16
240
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
241Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Ack
royd
et
al. (
2000
)95
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry U
K
Lang
uage
Eng
lish
Stud
y de
sign
R
CT
No.
of
part
icip
ants
Tota
l: 36
Inte
rven
tion:
18
Com
para
tor:
18N
o. o
f rec
ruit
ing
cent
res
Not
st
ated
Follo
w-u
p pe
riod
an
d fr
eque
ncy
FU a
t 1,
6, 1
2 an
d 24
mth
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y BO
– L
GD
Mai
n el
igib
ility
cri
teri
a Pa
tient
s w
ith L
GD
in
circ
umfe
rent
ial B
O o
f at
leas
t 3
cm in
leng
th, w
ho w
ere
rece
ivin
g om
epra
zole
wer
e el
igib
le. H
owev
er, h
isto
logi
cal
re-e
xam
inat
ion
afte
r bi
opsy
ha
d to
con
firm
the
dia
gnos
isPa
tien
t ch
arac
teri
stic
s%
Mal
e: 83
Age
ran
ge: 3
0–71
yrM
edia
n ag
e: 56
yrR
ange
of p
re-t
reat
men
t le
ngth
s of
Bar
rett
’s: 3
–15
cmC
onco
mit
ant
trea
tmen
t Pa
tient
s w
ere
give
n an
alge
sic
and
antie
met
ic d
rugs
as
requ
ired
follo
win
g tr
eatm
ent.
Patie
nts
wer
e al
so s
uppl
ied
with
ant
acid
s to
tak
e as
ne
eded
. Thr
ough
out
the
trea
tmen
t an
d FU
per
iod
patie
nts
wer
e m
aint
aine
d on
20
mg
omep
razo
le d
aily
Tria
l tre
atm
ents
ALA
–PD
T v
s Pl
aceb
o-PD
TIn
terv
enti
on P
atie
nts
dran
k 30
mg/
kg A
LA (
diss
olve
d in
50
ml o
f ora
nge
juic
e) fo
llow
ed 4
hr
late
r by
lase
r en
dosc
opy
(und
er in
trav
enou
s se
datio
n an
d an
alge
sia)
whe
n th
e ex
tent
of
Barr
ett’s
are
a w
as r
ecor
ded.
A c
oppe
r va
pour
lase
r de
liver
ed b
y a
fibre
with
a
diffu
ser
tip w
as u
sed
to d
eliv
er g
reen
lig
ht (
514
nm)
at a
pow
er d
ensi
ty o
f 12
0 m
W/c
m2 f
or 5
00 s
per
3-cm
leng
th.
All
patie
nts
had
two
sepa
rate
tre
atm
ents
(d
ista
l, th
en p
roxi
mal
, tot
al t
reat
men
t tim
e 10
00 s,
ene
rgy
dens
ity 6
0 J/c
m2 )
so
that
6 cm
of o
esop
hagu
s w
as t
reat
ed
(upp
er 6
cm o
f Bar
rett
’s m
ucos
a). T
his
repr
esen
ted
com
plet
e tr
eatm
ent
of
Barr
ett’s
epi
thel
ium
in o
ne-h
alf o
f the
pa
tient
s. Pa
tient
s re
mai
ned
in h
ospi
tal
until
dar
k, an
d w
ere
advi
sed
to a
void
br
ight
ligh
t fo
r 24
hr
Com
para
tor A
s fo
r ab
ove,
exc
ept
oran
ge ju
ice
alon
e w
as u
sed
as p
lace
bo
Mor
talit
y N
ot a
sses
sed
Mor
bidi
ty In
the
PD
T g
roup
16/
18
(89%
) sh
owed
mac
rosc
opic
evi
denc
e of
re
gres
sion
at
FU e
ndos
copy
, com
pare
d w
ith 2
/18
(11%
) in
the
pla
cebo
gro
up;
the
corr
espo
ndin
g m
edia
n re
duct
ion
in a
reas
wer
e 30
% fo
r PD
T v
s 0%
for
plac
ebo
(bot
h p
< 0.
001)
. All
regr
essi
on
case
s di
spla
yed
norm
al s
quam
ous
muc
osa
whe
n bi
opsi
ed. T
here
was
a r
educ
tion
in
prev
alen
ce o
f dys
plas
ia in
favo
ur o
f the
PD
T g
roup
(0/
18 v
s 12
/18,
p <
0.0
01).
Alth
ough
it w
as u
ncle
ar a
s to
whi
ch F
U
poin
t th
ese
resu
lts r
elat
e to
, the
aut
hors
di
d st
ate
that
the
effe
cts
of t
reat
men
t w
ere
mai
ntai
ned
for
up t
o 24
mth
AE
s All
PDT
pat
ient
s ex
peri
ence
d ch
est
pain
dur
ing
trea
tmen
t th
at p
ersi
sted
for
3–5
d, a
nd w
as a
ggra
vate
d by
sw
allo
win
g or
cou
ghin
g. O
ne p
atie
nt d
evel
oped
a
mild
ski
n ra
sh o
n ex
posu
re t
o su
nlig
ht
(res
olve
d w
ithin
48
hr).
No
patie
nts
com
plai
ned
of d
ysph
agia
. No
resu
lts
appe
ared
to
have
bee
n re
port
ed fo
r th
e pl
aceb
o gr
oup
Res
ourc
e us
e N
ot a
sses
sed
Aut
hors
’ con
clus
ions
ALA
–PD
T c
an
prov
ide
safe
and
effe
ctiv
e ab
latio
n of
low
-gr
ade
dysp
last
ic e
pith
eliu
mB
rief
stu
dy a
ppra
isal
Thi
s sm
all s
tudy
w
as g
ener
ally
wel
l con
duct
ed, a
nd t
he
resu
lts a
ppea
r re
liabl
e. H
owev
er, i
t sh
ould
be
not
ed t
hat
no r
esul
ts a
ppea
r to
hav
e be
en r
epor
ted
on A
Es in
the
pla
cebo
gr
oup,
and
it w
as u
ncle
ar t
o w
hich
FU
th
e m
ain
stud
y re
sults
rel
ate
BO, B
arre
tt’s
oeso
phag
us.
Appendix 16
240
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
241Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Ack
royd
et a
l. (1
996)
96
Dat
a so
urce
Abs
trac
tC
ount
ry U
KLa
ngua
ge E
nglis
hSt
udy
desi
gn R
CT
No.
of p
arti
cipa
nts
Tota
l: 28
Inte
rven
tion:
Not
sta
ted
Com
para
tor:
Not
sta
ted
No.
of r
ecru
itin
g ce
ntre
s N
ot s
tate
dFo
llow
-up
peri
od a
nd
freq
uenc
y N
ot s
tate
d
Trea
tmen
t in
tent
ion
Cur
ativ
e (d
osin
g st
udy)
Type
(s)
of c
ance
r an
d hi
stol
ogy
Dys
plas
tic B
OM
ain
elig
ibili
ty
crit
eria
Not
sta
ted
Pati
ent
char
acte
rist
ics
Not
st
ated
Con
com
itan
t tr
eatm
ent
Not
st
ated
Tria
l tre
atm
ents
ALA
–PD
T 3
0 m
g/kg
vs
ALA
–PD
T 5
0 m
g/kg
vs
plac
ebo
Inte
rven
tion
Ora
l ALA
at
30 o
r 50
mg/
kg, o
r pl
aceb
o, w
as fo
llow
ed 4
hr
late
r by
ligh
t ad
min
istr
atio
n. N
o fu
rthe
r pa
ram
eter
s w
ere
repo
rted
Com
para
tor
See
‘Inte
rven
tion’
2nd
com
para
tor
See
‘Inte
rven
tion’
Mor
talit
y N
ot a
sses
sed
Mor
bidi
ty N
ot a
sses
sed
AE
s In
the
30-
mg/
kg g
roup
, one
pat
ient
ha
d m
ild p
hoto
sens
itivi
ty, b
ut n
o ot
her
AEs
wer
e se
en. I
n th
e 50
-mg/
kg g
roup
, oe
soph
agea
l dis
com
fort
, hai
r lo
ss, a
nd
tran
sien
t di
stur
banc
e of
live
r fu
nctio
n te
st r
esul
ts w
ere
obse
rved
Res
ourc
e us
e N
ot a
sses
sed
Aut
hors
’ con
clus
ions
ALA
–PD
T
at 3
0 m
g/kg
sho
uld
prov
ide
optim
al
trea
tmen
t co
nditi
ons
in B
OB
rief
stu
dy a
ppra
isal
The
abs
ence
of
impo
rtan
t m
etho
dolo
gica
l, po
pula
tion,
an
d re
sult
deta
ils in
thi
s ab
stra
ct o
f a
smal
l stu
dy, m
eans
it is
diffi
cult
to
asse
ss t
he r
elia
bilit
y of
its
resu
lts
Appendix 16
242
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
243Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Hag
e et
al.
(200
4)97
Link
ed p
ublic
atio
ns19
8
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry T
he
Net
herl
ands
Lang
uage
Eng
lish
Stud
y de
sign
RC
TN
o. o
f par
tici
pant
sTo
tal:
40In
terv
entio
n: P
DT
20
+ 1
00: 1
3C
ompa
rato
r: PD
T10
0: 1
32n
d C
ompa
rato
r: A
PC: 1
4N
o. o
f rec
ruit
ing
cent
res
Not
sta
ted
Follo
w-u
p pe
riod
an
d fr
eque
ncy
6 w
k, 6,
12,
18
and
24 m
th
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y Pa
tient
s w
ith B
O
with
out
dysp
lasi
a or
with
LG
DM
ain
elig
ibili
ty c
rite
ria
Patie
nts
18 yr
or
over
with
BO
w
ithou
t dy
spla
sia
or w
ith L
GD
on
his
tolo
gica
l exa
min
atio
n w
ere
elig
ible
. Pat
ient
s ha
d to
hav
e a
BO
leng
th o
f 2–5
cm a
nd s
peci
alis
ed
inte
stin
al m
etap
lasi
a. A
ll pa
tient
s w
ere
taki
ng P
PIs
for
at le
ast
6 m
th
befo
re t
reat
men
t. Ex
clus
ion
crite
ria
wer
e in
tole
ranc
e to
(re
peat
ed)
endo
scop
y, pr
egna
ncy,
acut
e po
rphy
ria
and
inte
rcur
rent
dis
ease
s pr
eclu
ding
sur
viva
l dur
ing
the
stud
y pe
riod
Pati
ent
char
acte
rist
ics
% M
ale:
78M
edia
n ag
e: 59
yrA
ge r
ange
: 41–
72 yr
M
ean
BO le
ngth
: 3 cm
(ra
nge
2–5
cm)
Dys
plas
ia: N
one
32; L
GD
ei
ght
Con
com
itan
t tr
eatm
ent
If co
mpl
ete
elim
inat
ion
of B
O w
as
not
achi
eved
by
the
desi
gnat
ed
trea
tmen
t at
6 w
k, th
e re
mai
ning
BO
was
abl
ated
by
addi
tiona
l APC
w
ith a
max
imum
of t
wo
sess
ions
at
4-w
k in
terv
als.
Patie
nts
wer
e tr
eate
d w
ith a
dai
ly d
ose
of a
t le
ast
40 m
g of
om
epra
zole
for
the
dura
tion
of t
he s
tudy
. Mea
n do
se
47.5
mg
(ran
ge 4
0–80
mg)
Tria
l tre
atm
ents
PD
T w
ith
frac
tiona
ted
dose
(20
+ 1
00) A
LA v
s PD
T w
ith s
ingl
e-do
se A
LA v
s APC
Inte
rven
tion
Fra
ctio
nate
d PD
T:
60 m
g/kg
ALA
was
dis
solv
ed in
20
ml
of o
rang
e ju
ice.
All
patie
nts
wer
e ke
pt in
a d
arke
ned
room
for
36 h
r. A
KT
P/53
2 dy
e la
ser
mod
ule
was
us
ed t
o de
liver
ligh
t at
a w
avel
engt
h of
630
nm
. PD
T w
as p
erfo
rmed
w
ith a
flue
nce
of 2
0 J/c
m2 a
t 1
hr
and
100
J/cm
2 at
4 hr
afte
r ALA
ad
min
istr
atio
n. L
ight
del
iver
y w
as
perf
orm
ed u
sing
an
infla
tabl
e ba
lloon
w
ith a
n in
flate
d di
amet
er o
f 2.5
cm.
Cal
cula
ted
tota
l flue
nce
rate
was
10
0 m
W/c
m2
Com
para
tor
Sing
le-d
ose
ALA
–PD
T:
As
for
frac
tiona
ted
PDT
with
the
ex
cept
ion
that
the
re w
as a
sin
gle
illum
inat
ion
of 1
00 J/
cm2 a
t 4
hr a
fter
ALA
adm
inis
trat
ion
2nd
com
para
tor
APC
: an
Arg
on
Beam
er 2
dev
ice,
APC
300
was
use
d w
ith a
gas
flow
rat
e of
2 l/
min
at
a po
wer
set
ting
of 6
5 W. T
he a
im w
as t
o ab
late
tw
o-th
irds
of t
he o
esop
hage
al
circ
umfe
renc
e of
BO
dur
ing
the
1st
sess
ion
and
in t
he fo
llow
ing
sess
ion
to
abla
te t
he r
emai
nder
. APC
invo
lved
a
max
imum
of t
wo
trea
tmen
t se
ssio
ns
per
patie
nt a
t 4-
wk
inte
rval
s
Mor
talit
y N
ot a
sses
sed
Mor
bidi
ty A
t 6
wk,
mea
n en
dosc
opic
BO
sur
face
red
uctio
n w
as 5
1% (
rang
e 20
–100
%)
in t
he s
ingl
e do
se P
DT
gr
oup,
86%
(ra
nge
0–10
0%)
in t
he
frac
tiona
ted
PDT
gro
up a
nd 9
3%
(ran
ge 4
0–10
0%)
in t
he A
PC g
roup
. T
his
was
sta
tistic
ally
sig
nific
ant
for
the
com
pari
son
betw
een
sing
le-d
ose
PDT
and
frac
tiona
ted
dose
PD
T a
nd
sing
le-d
ose
PDT
and
APC
. Diff
eren
ces
betw
een
frac
tiona
ted
dose
PD
T a
nd
APC
wer
e no
t si
gnifi
cant
. Rat
es o
f co
mpl
ete
abla
tion
wer
e ns
bet
wee
n th
e gr
oups
. 6-,
12-
and
18-m
th d
ata
not
extr
acte
d as
pat
ient
s w
ere
then
el
igib
le t
o re
ceiv
e A
PCA
Es
23 o
f 26
patie
nts
acro
ss t
he
two
PDT
gro
ups
and
five
of 1
4 in
the
A
PC g
roup
exp
erie
nced
pai
n du
ring
tr
eatm
ent
(p <
0.0
1). T
here
wer
e m
ore
case
s of
nau
sea
and
vom
iting
w
ith P
DT
(7
vs 0
in A
PC, p
< 0
.05)
an
d pa
tient
s ha
d m
ore
elev
ated
live
r en
zym
e re
sults
in t
ests
(20
vs
0,
p <
0.01
). D
iffer
ence
s in
ody
noph
agia
, fe
ver,
sudd
en d
eath
and
str
ictu
re
form
atio
n w
ere
not
sign
ifica
ntR
esou
rce
use
Not
ass
esse
d
Aut
hors
’ con
clus
ions
APC
alo
ne
or A
LA–P
DT
in c
ombi
natio
n w
ith
APC
can
lead
to
com
plet
e re
vers
al o
f Ba
rret
t’s e
pith
eliu
m in
at
leas
t tw
o-th
irds
of p
atie
nts
whe
n ad
min
iste
red
in m
ultip
le t
reat
men
t se
ssio
ns. T
he
auth
ors
did
not
reco
mm
end
use
of
thes
e te
chni
ques
for
prop
hyla
ctic
ab
latio
n of
BO
Bri
ef s
tudy
app
rais
al T
his
was
a
smal
l tri
al a
nd t
he lo
w n
umbe
rs o
f pa
tient
s ac
ross
the
thr
ee g
roup
s m
ay
have
mea
nt t
here
was
insu
ffici
ent
pow
er t
o de
tect
tre
atm
ent
diffe
renc
es
whe
re t
hey
exis
ted.
A fu
rthe
r pr
oble
m
is t
hat
all p
atie
nts
who
did
not
re
spon
d ad
equa
tely
wer
e gi
ven
APC
, so
the
long
-ter
m e
ffect
of P
DT
alo
ne
is u
ncle
ar
Appendix 16
242
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
243Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Kel
ty e
t al
. (20
04)10
2
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry U
KLa
ngua
ge E
nglis
hSt
udy
desi
gn
RC
TN
o. o
f pa
rtic
ipan
tsTo
tal:
25
Inte
rven
tion:
Fiv
eC
ompa
rato
r: Fi
ve2n
d C
ompa
rato
r: Fi
ve3r
d C
ompa
rato
r: Fi
ve4t
h C
ompa
rato
r: Fi
veN
o. o
f rec
ruit
ing
cent
res
One
Follo
w-u
p pe
riod
an
d fr
eque
ncy
4 w
k
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y N
on-d
yspl
astic
BO
Mai
n el
igib
ility
cr
iter
ia P
atie
nts
alre
ady
part
icip
atin
g in
a la
rge
coho
rt
stud
y on
BO
with
bi
opsy
pro
ven
Barr
ett’s
epi
thel
ium
Pati
ent
char
acte
rist
ics
% M
ale:
80M
edia
n ag
e: 63
yr
Age
ran
ge: 3
1–81
yrM
edia
n le
ngth
of
Barr
ett’s
epi
thel
ium
w
as 4
cm (
rang
e 2–
15 cm
), no
pat
ient
s ha
d hi
gh o
r LG
D o
n bi
opsy
Con
com
itan
t tr
eatm
ent
40 m
g es
omep
razo
le d
aily
Tria
l tre
atm
ents
ALA
–PD
T a
t va
riou
s do
ses
(30
mg/
kg o
r 60
mg/
kg)
at 4
- or
6-
hr in
cuba
tion
times
or
with
frac
tiona
ted
illum
inat
ion
Inte
rven
tion
30
mg/
kg A
LA–P
DT,
light
de
liver
ed b
y en
dosc
opy
afte
r 4-
hr P
DT
pr
otoc
ol: A
LA d
isso
lved
in 5
0 m
l of o
rang
e ju
ice
and
take
n or
ally.
Pat
ient
s ke
pt in
dim
ly
lit r
oom
pri
or t
o tr
eatm
ent.
At
appr
opri
ate
time
patie
nts
unde
rwen
t en
dosc
opy
with
in
trav
enou
s se
datio
n, a
nalg
esia
and
an
antie
met
ic d
rug.
Ballo
on a
pplic
ator
was
pl
aced
ove
r a
guid
ewire
in t
he o
esop
hagu
s an
d po
sitio
n co
nfirm
ed e
ndos
copi
cally
. Ba
lloon
was
infla
ted
to a
roun
d 20
mm
Hg
and
light
del
iver
ed b
y a
5-cm
cyl
indr
ical
di
ffuse
r fib
re. R
ed li
ght
(635
nm
, 2W
di
ode
lase
r) w
as u
sed
at fl
uenc
e ra
te o
f 68
mW
/cm
2 for
a t
otal
dos
e of
85
J/cm
2 . Pa
tient
s re
cove
red
in a
dim
ly li
t ro
om,
disc
harg
ed w
ith o
ral a
nalg
esia
and
adv
ice
to
avoi
d br
ight
ligh
ts fo
r 24
hr
Com
para
tor
30 m
g/kg
ALA
–PD
T, lig
ht
deliv
ered
by
endo
scop
y af
ter
6 hr
2nd
com
para
tor
30 m
g/kg
ALA
–PD
T
repe
ated
at
2 hr
, lig
ht d
eliv
ered
by
endo
scop
y af
ter
4 hr
3rd
com
para
tor
60 m
g/kg
ALA
–PD
T, lig
ht
deliv
ered
by
endo
scop
y af
ter
4 hr
4th
com
para
tor
60 m
g/kg
ALA
–PD
T, lig
ht
deliv
ered
by
endo
scop
y af
ter
6 hr
Mor
talit
y N
ot a
sses
sed
Mor
bidi
ty A
t 1
mth
FU
all
patie
nts
show
ed a
red
uctio
n in
the
are
a of
Bar
rett
’s ep
ithel
ium
in t
he t
reat
ed a
rea,
med
ian
redu
ctio
n fo
r al
l 25
patie
nts
was
60%
. M
edia
n re
duct
ion
in a
rea
vari
ed b
etw
een
30%
and
60%
for
each
tre
atm
ent
grou
p. T
he g
reat
est
redu
ctio
ns w
ere
seen
in t
he
frac
tiona
ted
and
30 m
g/kg
gro
ups
(all
60%
), bu
t th
is d
iffer
ence
was
not
sta
tistic
ally
si
gnifi
cant
AE
s N
o m
ajor
AEs
– n
o pe
rfor
atio
ns o
r st
rict
ures
. Sig
nific
ant
N&
V o
ccur
red
in
32%
of p
atie
nts
who
req
uire
d fu
rthe
r an
ti-em
etic
tre
atm
ent.
N&
V w
as m
ore
com
mon
in
pat
ient
s w
ho r
ecei
ved
the
high
er d
ose
of A
LA. F
ive
patie
nts
had
a do
cum
ente
d ph
otos
ensi
tivity
rea
ctio
n –
all w
ere
mild
ca
ses
Res
ourc
e us
e N
ot a
sses
sed
Aut
hors
’ con
clus
ions
Low
dos
e A
LA–
PDT
app
ears
to
be a
saf
e pr
otoc
ol fo
r th
e ab
latio
n of
BO
. The
aut
hors
rec
omm
end
that
ALA
sho
uld
be g
iven
ora
lly a
s 30
mg/
kg
4- t
o 6-
hr b
efor
e ac
tivat
ion
and
coul
d be
ta
ken
at h
ome
Bri
ef s
tudy
app
rais
al T
his
was
a s
mal
l st
udy
that
aim
ed t
o es
tabl
ish
optim
um
dosa
ge r
egim
es. A
lthou
gh p
atie
nts
wer
e ra
ndom
ised
to
trea
tmen
t, no
info
rmat
ion
on b
lindi
ng o
r al
loca
tion
conc
ealm
ent
was
pro
vide
d. T
he s
ampl
e si
ze a
ppea
rs t
o ha
ve b
een
too
smal
l to
view
the
aut
hors
’ co
nclu
sion
s as
bei
ng r
elia
ble
Appendix 16
244
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
245Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Kel
ty e
t al.
(200
4)98
Link
ed
publ
icat
ions
199–
201
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry U
KLa
ngua
ge E
nglis
hSt
udy
desi
gn R
CT
No.
of p
arti
cipa
nts
Tota
l: 72
Inte
rven
tion:
35
(PD
T)
Com
para
tor:
37
(APC
)N
o. o
f rec
ruit
ing
cent
res
One
Follo
w-u
p pe
riod
an
d fr
eque
ncy
1 da
y, 4
wk
then
6, 1
2 an
d 24
mth
afte
r su
cces
sful
tre
atm
ent
or fi
ve s
essi
ons
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y BO
Mai
n el
igib
ility
cr
iter
ia P
atie
nts
wer
e in
vite
d to
ta
ke p
art
from
an
end
osco
pic
scre
enin
g pr
ogra
mm
e (o
ver
150
wer
e ap
proa
ched
). N
o fu
rthe
r de
tails
re
port
edPa
tien
t ch
arac
teri
stic
s%
Mal
e: 81
Age
ran
ge: 2
8–83
yr
Med
ian
age:
61 yr
All
patie
nts
had
biop
sy p
rove
n Ba
rret
t’s e
pith
eliu
m
(med
ian
leng
th o
f 4
cm, r
ange
2–1
5cm
). N
o pa
tient
s ha
d hi
gh
or L
GD
Con
com
itan
t tr
eatm
ent
40 m
g es
omep
razo
le d
aily,
w
ith o
ral a
nalg
esia
as
requ
ired
Tria
l tre
atm
ents
ALA
–PD
T v
s APC
Inte
rven
tion
ALA
–PD
T: 3
0 m
g/kg
of A
LA
diss
olve
d in
50
ml o
f ora
nge
juic
e ta
ken
oral
ly, p
atie
nt k
ept
in a
dim
roo
m p
rior
to
tre
atm
ent
(46
hr la
ter)
. End
osco
py w
as
carr
ied
out
(with
intr
aven
ous
seda
tion,
an
alge
sia
and
an a
ntie
met
ic)
and
a ba
lloon
ap
plic
ator
was
pla
ced
over
a g
uide
wire
(p
ositi
on c
onfir
med
end
osco
pica
lly)
and
infla
ted
to a
ppro
xim
atel
y 20
mm
Hg.
Ligh
t w
as d
eliv
ered
usi
ng a
cyl
indr
ical
diff
user
fib
re –
red
lase
r lig
ht (
635
nm 3
W)
at a
flu
ence
rat
e of
68
mW
/cm
2 and
tot
al li
ght
dose
of 8
5 J/c
m2 .
Patie
nts
wer
e di
scha
rged
an
d ad
vise
d to
avo
id b
righ
t lig
hts
for
24 h
r. Fo
llow
-up
at 4
wk
– if
resi
dual
Bar
rett
’s ep
ithel
ium
pat
ient
was
re-
trea
ted
until
re
-epi
thel
isat
ion
was
com
plet
e or
to
a m
axim
um o
f five
tre
atm
ents
Com
para
tor A
PC: e
ndos
copy
as
per
PDT
pr
otoc
ol. A
PC g
ener
ator
set
with
gas
flow
of
2 l/
min
and
pow
er s
ettin
g of
65 W
. APC
pr
obe
pass
ed d
own
biop
sy c
hann
el a
nd
posi
tione
d w
ith t
ip o
f pro
be 1
cm d
ista
l to
the
end
of t
he s
cope
. APC
per
form
ed in
a
linea
r fa
shio
n co
agul
atin
g st
rips
of t
issu
e ap
prox
imat
ely
2 m
m w
ide
at e
ach
pass
. O
ne-h
alf o
f the
affe
cted
circ
umfe
renc
e w
as
trea
ted
at a
ny o
ne s
ittin
g on
the
rat
iona
le
of r
educ
ing
chan
ces
of s
tric
ture
. Rep
eat
trea
tmen
t as
per
PD
T b
ut u
sing
APC
Mor
talit
y N
ot a
sses
sed
Mor
bidi
ty S
igni
fican
tly fe
wer
tre
atm
ents
w
ere
perf
orm
ed in
the
APC
gro
up (
med
ian
3) t
han
in t
he P
DT
gro
up (
med
ian
5),
p =
0.01
6. T
he m
edia
n nu
mbe
r of
tre
atm
ents
re
quire
d fo
r su
cces
sful
abl
atio
n w
as t
wo
in
the
PDT
gro
up a
nd t
hree
in t
he A
PC g
roup
, p
= 0.
189
Com
plet
e m
acro
scop
ic r
ever
sal o
f the
co
lum
nar
segm
ent
to s
quam
ous
epith
eliu
m
was
ach
ieve
d in
50%
of P
DT
pat
ient
s an
d 97
% o
f APC
pat
ient
s, p
< 0.
0001
AE
s M
ajor
sid
e ef
fect
s fo
r PD
T w
ere
min
imal
with
no
stri
ctur
es o
r pe
rfor
atio
ns.
Sign
ifica
nt N
&V
occ
urre
d in
32%
of
patie
nts
who
req
uire
d fu
rthe
r an
tiem
etic
tr
eatm
ent.
Five
pat
ient
s re
port
ed c
utan
eous
ph
otos
ensi
tivity
(m
ild e
ryth
ema
and
pain
). A
ll A
PC p
atie
nts
repo
rted
dis
com
fort
an
d 91
% r
epor
ted
tran
sien
t dy
spha
gia
and
odyn
opha
gia.
All
wer
e re
solv
ed w
ith
oral
ana
lges
ia o
ver
3 d.
No
oeso
phag
eal
perf
orat
ions
occ
urre
d, o
ne p
atie
nt
deve
lope
d dy
spha
gia
to s
olid
s an
d re
quire
d fo
ur d
ilata
tions
Res
ourc
e us
e N
ot a
sses
sed
Aut
hors
’ con
clus
ions
PD
T a
nd A
PC a
re
both
effe
ctiv
e fo
r ab
latin
g BO
. APC
app
ears
m
ore
effe
ctiv
e bu
t la
rger
stu
dies
sho
uld
asse
ss im
pact
on
carc
inom
a de
velo
pmen
tB
rief
stu
dy a
ppra
isal
Thi
s w
as a
re
lativ
ely
robu
st c
ompa
rativ
e tr
ial (
desp
ite
the
sam
ple
size
), w
hich
wou
ld a
lso
have
be
nefit
ed fr
om t
he u
se o
f blin
ded
outc
ome
asse
ssor
s. H
owev
er, t
his
stud
y, lik
e its
re
late
d do
sing
stu
dy10
2 was
of B
O p
atie
nts
with
out
dysp
lasi
a; su
ch p
atie
nts
are
ofte
n no
t tr
eate
d at
all,
so t
he r
esul
ts a
ppea
r to
be
of li
mite
d us
e in
rel
atio
n to
clin
ical
pr
actic
e
Appendix 16
244
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
245Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Mac
kenz
ie e
t al.
(200
8)10
5
Link
ed p
ublic
atio
ns20
2–20
4
Dat
a so
urce
Ful
l pap
erC
ount
ry U
KLa
ngua
ge E
nglis
hSt
udy
desi
gn R
CT
No.
of p
arti
cipa
nts
Tota
l: 27
Inte
rven
tion
(ALA
w
ith r
ed li
ght)
: 14
Com
para
tor:
(ALA
with
gre
en
light
): 13
No.
of r
ecru
itin
g ce
ntre
s O
neFo
llow
-up
peri
od a
nd
freq
uenc
y 4
wk
then
eve
ry
3 m
th fo
r th
e 1s
t ye
ar t
hen
ever
y 6
mth
for
the
2nd
year
, th
en y
earl
y
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y BO
w
ith H
GD
Mai
n el
igib
ility
cr
iter
ia P
atie
nts
with
BO
with
HG
D.
Patie
nts
wer
e no
t al
low
ed t
o re
ceiv
e ch
emot
hera
py o
r ra
diot
hera
py w
ithin
1
mth
pri
or t
o PD
T. O
ther
exc
lusi
on
crite
ria
wer
e pr
ovid
edPa
tien
t ch
arac
teri
stic
s N
ot
stat
edC
onco
mit
ant
trea
tmen
t A
ll pa
tient
s re
ceiv
ed P
PIs.
Intr
aven
ous
fluid
s an
d an
tiem
etic
s w
ere
give
n pr
e-op
erat
ivel
y
Tria
l tre
atm
ents
ALA
–PD
T w
ith r
ed
light
vs A
LA–P
DT
with
gre
en li
ght
Inte
rven
tion
Phas
e 1
(eig
ht p
atie
nts)
ALA
with
red
ligh
t: at
635
nm
del
iver
ing
a do
se o
f 200
J/cm
2. L
aser
tre
atm
ent
was
app
lied
4 hr
afte
r or
al A
LA
adm
inis
trat
ion
(30
mg/
kg).
Patie
nts
rece
ived
up
to t
hree
tre
atm
ents
with
PD
T 1
mth
apa
rtPh
ase
2 (s
ix p
atie
nts)
As
abov
e bu
t w
ith 6
0 m
g/kg
ALA
Com
para
tor
Phas
e 1
(eig
ht p
atie
nts)
ALA
with
gre
en li
ght
at 5
12 n
m
othe
rwis
e as
for
inte
rven
tion
Phas
e 2
(five
pat
ient
s)A
s ab
ove
but
with
60
mg/
kg A
LA
Mor
talit
y N
ot a
sses
sed
Mor
bidi
tyPh
ase
14
of 1
6 pa
tient
s (2
5%)
had
HG
D
erad
icat
ed (
thre
e re
d lig
ht, o
ne g
reen
lig
ht)
The
tri
al w
as p
ause
d fo
llow
ing
inte
rim
an
alys
is. I
t th
en p
roce
eded
to
Phas
e 2
Phas
e 2
Six
of s
ix p
atie
nts
in t
he 6
0-m
g re
d lig
ht g
roup
had
suc
cess
ful t
reat
men
t, w
here
as o
ne o
f five
was
suc
cess
ful i
n th
e 60
-mg
gree
n lig
ht g
roup
(p
= 0.
01)
60-m
g A
LA r
ed li
ght
was
als
o m
ore
succ
essf
ul t
han
30-m
g A
LA r
ed li
ght
(p =
0.0
3) a
nd t
han
30 m
g A
LA g
reen
lig
ht (
p =
0.00
5)A
Es A
Es w
ere
not
all r
epor
ted
by
grou
p. A
ll pa
tient
s re
ceiv
ing
60 m
g PD
T s
how
ed m
inor
, sel
f-lim
iting
ab
norm
aliti
es in
the
res
ults
of t
heir
liv
er fu
nctio
n te
sts
Res
ourc
e us
eN
ot a
sses
sed
Aut
hors
’ con
clus
ions
PD
T w
ith
ALA
at
30 m
g/kg
with
gre
en o
r re
d la
ser
is in
effe
ctiv
e fo
r er
adic
atio
n of
H
GD
in B
O. A
LA a
t 60
mg/
kg a
ctiv
ated
by
100
0 J/c
m r
ed la
ser
light
has
hig
h ef
ficac
y fo
r H
GD
in B
OB
rief
stu
dy a
ppra
isal
Thi
s tr
ial,
alth
ough
sm
all,
was
abl
e to
sug
gest
a
grea
ter
effe
ctiv
enes
s w
ith 6
0 m
g re
d lig
ht. S
uch
findi
ngs
wou
ld n
eed
to b
e co
nfirm
ed in
larg
er t
rial
s an
d an
y A
Es
docu
men
ted
Appendix 16
246
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
247Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Mac
kenz
ie
et a
l. (20
08)10
4
Dat
a so
urce
A
bstr
act
Cou
ntry
UK
Lang
uage
Eng
lish
Stud
y de
sign
RC
TN
o. o
f par
tici
pant
sTo
tal:
40 r
ecru
ited
of a
pla
nned
66.
32
wer
e tr
eate
dIn
terv
entio
n: A
LA–
PDT:
16
Com
para
tor:
PDT
w
ith P
hoto
frin
: 16
No.
of r
ecru
itin
g ce
ntre
s N
ot s
tate
dFo
llow
-up
peri
od
and
freq
uenc
y 6
wk,
4 m
th a
nd 1
yr
post
the
rapy
Trea
tmen
t in
tent
ion
Not
st
ated
Type
(s)
of c
ance
r an
d hi
stol
ogy
BO
with
HG
DM
ain
elig
ibili
ty
crit
eria
Pat
ient
s w
ith B
O w
ith
HG
D c
onfir
med
by
two
inde
pend
ent
path
olog
ists
wer
e el
igib
le fo
r th
e tr
ial.
Any
vis
ible
nod
ules
of
HG
D w
ere
rem
oved
an
d pa
tient
s on
ly
trea
ted
if re
sidu
al
HG
D w
as s
till
pres
ent
Pati
ent
char
acte
rist
ics
Not
st
ated
Con
com
itan
t tr
eatm
ent
Not
st
ated
Tria
l tre
atm
ents
ALA
–PD
T v
s PD
T w
ith P
hoto
frin
Inte
rven
tion
60
mg/
kg A
LA
activ
ated
by
1178
J/cm
of r
ed
lase
r lig
htC
ompa
rato
r Ph
otof
rin
PDT
with
the
sta
ndar
d pr
otoc
ol o
r as
pre
viou
sly
show
n to
be
the
mos
t ef
fect
ive
(no
furt
her
deta
ils
give
n)
Mor
talit
y N
ot a
sses
sed
Mor
bidi
ty F
ive
patie
nts
are
unde
rgoi
ng r
epea
t th
erap
y (t
hree
Ph
otof
rin,
tw
o A
LA).
Rem
issi
on r
ates
ar
e 14
of 1
4 (1
00%
) in
the
ALA
–PD
T
grou
p an
d ni
ne o
f 14
(64%
) in
the
Ph
otof
rin
grou
p (p
< 0
.05)
AE
s St
rict
ures
dev
elop
ed in
six
of 1
6 pa
tient
s tr
eate
d w
ith P
hoto
frin
and
on
e of
16
trea
ted
with
ALA
(pr
obab
ly
not
rela
ted
to t
reat
men
t), p
< 0
.05.
Sk
in p
hoto
sens
itivi
ty d
evel
oped
in
seve
n of
16
patie
nts
trea
ted
with
Ph
otof
rin,
one
of w
hom
had
to
be
brie
fly a
dmitt
ed t
o ho
spita
l. N
o in
stan
ces
of p
hoto
sens
itisa
tion
wer
e fo
und
with
ALA
(p
< 0.
05). T
here
w
ere
no o
ther
sig
nific
ant
diffe
renc
es
betw
een
grou
ps r
egar
ding
sid
e ef
fect
sR
esou
rce
use
Not
ass
esse
d
Aut
hors
’ con
clus
ions
The
pre
limin
ary
data
sug
gest
tha
t A
LA–P
DT
is b
oth
safe
r an
d po
tent
ially
mor
e ef
fect
ive
than
PD
T w
ith P
hoto
frin
but
FU
is s
hort
and
not
all
patie
nts
in t
he
tria
l hav
e be
en t
reat
ed a
s ye
tB
rief
stu
dy a
ppra
isal
Thi
s tr
ial w
as r
epor
ted
in a
bstr
act
form
onl
y so
full
deta
ils o
f the
met
hods
are
not
ava
ilabl
e. T
he
data
pre
sent
ed a
re p
rom
isin
g bu
t w
ould
nee
d co
nfirm
atio
n in
lo
nger
FU
and
with
all
the
plan
ned
patie
nts
trea
ted
Appendix 16
246
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
247
Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Mac
kenz
ie e
t al.
(200
7)10
3
Link
ed p
ublic
atio
ns20
5
Dat
a so
urce
Abs
trac
tC
ount
ry U
KLa
ngua
ge E
nglis
hSt
udy
desi
gn R
CT
No.
of p
arti
cipa
nts
Tota
l: 24
app
eare
d to
hav
e be
en r
ando
mis
ed t
o ei
ther
re
d or
gre
en li
ght
and
wer
e pa
rt o
f a la
rger
stu
dy o
f 72
patie
nts
Inte
rven
tion:
Hig
h-do
se A
LA
(60
mg/
kg)
with
hig
h-do
se r
ed
or g
reen
ligh
t (1
000
J/cm
) –
not
stat
edC
ompa
rato
r: H
igh-
dose
ALA
(6
0 m
g/kg
) w
ith lo
w-d
ose
red
light
(50
0–70
0 J/c
m)
– no
t st
ated
2nd
Com
para
tor:
Low
-dos
e A
LA (
30 m
g/kg
) w
ith h
igh-
dose
red
or
gree
n lig
ht
(100
0 J/c
m)
– no
t st
ated
No.
of r
ecru
itin
g ce
ntre
s N
ot s
tate
dFo
llow
-up
peri
od a
nd
freq
uenc
y 36
mth
Trea
tmen
t in
tent
ion
Not
sta
ted
Type
(s)
of c
ance
r an
d hi
stol
ogy
BO w
ith
HG
DM
ain
elig
ibili
ty
crit
eria
Not
sta
ted
Pati
ent
char
acte
rist
ics
Not
st
ated
Con
com
itan
t tr
eatm
ent
Not
sta
ted
Tria
l tre
atm
ents
Hig
h-do
se A
LA
(60
mg/
kg)
with
Hig
h-do
se r
ed o
r gr
een
light
(10
00 J/
cm)
vs H
igh-
dose
A
LA (
60 m
g/kg
) w
ith lo
w-d
ose
red
light
(50
0–70
0 J/c
m)
vs L
ow-d
ose
ALA
(30
mg/
kg)
with
hig
h-do
se r
ed
or g
reen
ligh
t (1
000
J/cm
)In
terv
enti
on H
igh-
dose
ALA
(6
0 m
g/kg
) w
ith h
igh-
dose
red
or
gree
n lig
ht (
1000
J/cm
)C
ompa
rato
r H
igh-
dose
ALA
(6
0 m
g/kg
) w
ith lo
w-d
ose
red
light
(5
00–7
00 J/
cm)
2nd
com
para
tor
Low
-dos
e A
LA
(30
mg/
kg)
with
hig
h-do
se r
ed o
r gr
een
light
(10
00 J/
cm)
Mor
talit
y N
ot a
sses
sed
Mor
bidi
ty P
atie
nts
in t
he g
roup
rec
eivi
ng
Hig
h-do
se A
LA–P
DT
and
Hig
h-do
se r
ed
light
had
a s
igni
fican
t de
crea
se in
can
cer
risk
w
hen
com
pare
d w
ith t
he o
ther
tre
atm
ent
grou
ps a
t 36
mth
(24
% r
isk
vs 3
%). T
he
diffe
renc
e in
ade
noca
rcin
oma
rate
s w
ere
sign
ifica
nt w
hen
red
light
was
com
pare
d w
ith g
reen
(8%
vs
45%
, p <
0.0
5)A
Es
No
patie
nts
suffe
red
phot
osen
sitiv
ity
reac
tions
or
deve
lope
d oe
soph
agea
l st
rict
ures
Res
ourc
e us
e N
ot a
sses
sed
Aut
hors
’ con
clus
ions
The
dat
a fr
om t
his
tria
l sup
port
the
use
of
the
optim
al r
egim
en o
f ALA
in a
R
CT
of A
LA v
s Ph
otof
rin
PDT
Bri
ef s
tudy
app
rais
al T
his
smal
l st
udy
is r
epor
ted
in a
bstr
act
form
on
ly a
nd n
o fu
rthe
r pu
blic
atio
n is
av
aila
ble.
It is
, the
refo
re, d
ifficu
lt to
as
sess
the
qua
lity
of t
he t
rial
and
th
e re
liabi
lity
of t
he fi
ndin
gs
Appendix 16
248 Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
O
verh
olt
et a
l. (2
007)
99
Link
ed
publ
icat
ions
206–
209
Dat
a so
urce
Fu
ll pu
blis
hed
pape
rC
ount
ry N
ot
stat
edLa
ngua
ge
Engl
ish
Stud
y de
sign
R
CT
No.
of
part
icip
ants
Tota
l: 20
8 (6
1 in
lo
ng-t
erm
pha
se
grou
p)In
terv
entio
n:
PHO
PDT:
138
(4
8 in
long
-ter
m
phas
e gr
oup)
Com
para
tor:
OM
: 70
(13
in
long
ter
m p
hase
gr
oup)
No.
of
recr
uiti
ng
cent
res
30 (
in
four
unn
amed
co
untr
ies)
Follo
w-u
p pe
riod
and
fr
eque
ncy
Ever
y 3
mth
unt
il fo
ur c
onse
cutiv
e bi
opsy
res
ults
w
ere
nega
tive
for
HG
D, t
hen
bian
nual
ly u
ntil
5 yr
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y BO
with
H
GD
Mai
n el
igib
ility
cr
iter
ia P
atie
nts
wer
e el
igib
le if
the
y w
ere
diag
nose
d w
ith B
O
with
HG
D p
rove
n by
bi
opsy
and
be ≥
18yr
. Ex
clus
ion
crite
ria
wer
e: ca
ncer
oth
er t
han
non-
mel
anom
a sk
in c
ance
r w
ithin
the
last
5yr
; pri
or
PDT
to
the
oeso
phag
us,
oeso
phag
eal s
tric
ture
s un
resp
onsi
ve t
o di
lata
tion
and
furt
her
crite
ria
deta
iled
in fu
ll in
th
e pa
per
Pati
ent
char
acte
rist
ics
% M
ale:
85M
ean
age:
67 yr
Furt
her
patie
nt
char
acte
rist
ics
wer
e re
port
edC
onco
mit
ant
trea
tmen
t 9%
of
patie
nts
in th
e PH
OPD
T
grou
p un
derw
ent
an
oeso
phag
ecto
my
or
othe
r en
dosc
opic
ab
latio
n (3
%).
19%
of
the
pat
ient
s in
th
e O
M g
roup
had
PH
OPD
T t
reat
men
t, 10
% u
nder
wen
t an
oe
soph
agec
tom
y an
d 2.
9% h
ad a
noth
er
endo
scop
ic a
blat
ion
tech
niqu
e
Tria
l tre
atm
ents
PD
T
with
PH
OPD
T v
s O
M
alon
e In
terv
enti
on P
HO
PDT:
Pa
tient
s in
thi
s ar
m
rece
ived
a m
axim
um o
f th
ree
cour
ses
of P
DT
ove
r 5
yr s
epar
ated
by
at le
ast
3 m
th. O
ne c
ours
e of
PD
T
cons
iste
d of
a 2
-mg/
kg
PHO
inje
ctio
n fo
llow
ed
by o
ne la
ser
light
ses
sion
(6
30 n
m)
appl
ied
to t
he
oeso
phag
eal s
egm
ent
with
HG
D 4
0–50
hr
afte
r in
ject
ion.
The
ligh
t do
se
was
130
J/cm
of d
iffus
er
leng
th w
ith a
cen
trin
g ba
lloon
. A 2
nd li
ght
appl
icat
ion
of 5
0 J/c
m
with
out
the
cant
erin
g ba
lloon
cou
ld b
e gi
ven
96–1
20hr
afte
r PH
O
inje
ctio
n bu
t on
ly fo
r ar
eas
with
insu
ffici
ent
muc
osal
re
spon
se a
fter
the
1st
light
ap
plic
atio
n. A
max
imum
of
7 cm
of B
O w
as t
reat
ed
duri
ng o
ne c
ours
e of
PD
T. It
was
req
uire
d th
at t
he
entir
e le
ngth
of B
arre
tt’s
muc
osa
be t
reat
ed. P
atie
nts
also
rec
eive
d 20
mg
of O
M
twic
e da
ily. P
atie
nts
had
to
avoi
d ex
posu
re o
f eye
s an
d sk
in t
o di
rect
sun
light
and
hi
gh in
tens
ity li
ght
for
at
leas
t 30
d. T
hey
wer
e to
ld
to w
ear
dark
sun
glas
ses
for
a 30
-d p
erio
d w
hen
outd
oors
Com
para
tor
OM
: Pa
tient
s re
ceiv
ed 2
0 m
g O
M t
wic
e da
ily
Mor
talit
y Tw
o pa
tient
s in
the
PH
OPD
T a
nd o
ne p
atie
nt in
the
OM
gro
up d
ied
with
in t
he 1
st 2
yr fr
om e
vent
s un
rela
ted
to B
arre
tt’s
dise
ase.
No
deat
hs w
ere
rela
ted
to t
he t
reat
men
t. T
here
wer
e no
add
ition
al p
atie
nts
who
die
d ov
er t
he
cour
se o
f the
add
ition
al 3
yr o
f FU
Mor
bidi
ty T
he p
ropo
rtio
n of
res
pond
ers
(com
plet
e ab
latio
n of
HG
D)
was
si
gnifi
cant
ly h
ighe
r in
PH
OPD
T t
han
with
OM
(77
% v
s 39
%, p
< 0
.000
1). O
f the
om
epra
zole
alo
ne r
espo
nder
s th
ere
wer
e 26
% o
f the
PH
OPD
T a
nd 5
2% o
f th
e O
M p
atie
nts
who
ter
min
ated
the
tri
al w
ith e
ither
HG
D o
r ca
ncer
. Ana
lysi
s of
res
pond
ers
for
both
tre
atm
ent
grou
ps a
t 10
spe
cific
tim
e po
ints
sho
wed
a
prop
ortio
n of
res
pond
ers
alm
ost
twic
e as
larg
e in
PH
OPD
T c
ompa
red
with
OM
at
all a
sses
smen
t pe
riod
s (d
ata
not
show
n). T
here
was
a s
igni
fican
t di
ffere
nce
betw
een
the
med
ian
time
to C
R in
the
2 g
roup
s: PH
OPD
T, 11
3 d
and
OM
, 551
d, p
< 0
.000
1. O
ver
the
tria
l per
iod
10%
of P
HO
PDT
pat
ient
s ha
d H
GD
com
pare
d w
ith 3
1% o
f the
OM
pat
ient
sBy
the
end
of t
he 5
-yea
r FU
per
iod,
the
pro
babi
lity
of m
aint
aini
ng c
ompl
ete
abla
tion
of H
GD
was
48%
in P
HO
PDT
com
pare
d w
ith 4
% in
OM
, p <
0.0
001.
T
he m
edia
n du
ratio
n of
the
CR
was
44.
8 m
th in
the
PH
OPD
T g
roup
and
3.
2 m
th in
the
OM
gro
up. A
2-y
r re
spon
der
in t
he P
HO
PDT
gro
up h
ad a
90%
ch
ance
of m
aint
aini
ng t
he r
espo
nse
for
5 yr
com
pare
d w
ith 3
0% fo
r a
2-yr
re
spon
der
in t
he O
M g
roup
. Com
pari
son
betw
een
the
2 gr
oups
sho
wed
tha
t pa
tient
s in
the
PH
OPD
T g
roup
had
a s
igni
fican
t de
lay
in p
rogr
essi
on t
o ca
ncer
co
mpa
red
with
pat
ient
s in
the
OM
gro
up. I
n th
e PH
OPD
T g
roup
, 21
(15%
) pa
tient
s pr
ogre
ssed
to
canc
er fr
om d
48 t
o 17
93. I
n th
e O
M g
roup
, 20
(29%
) pa
tient
s pr
ogre
ssed
to
canc
er fr
om d
63 t
o 10
92. A
fter
5yr
of F
U, t
he r
ate
of
patie
nts
who
pro
gres
sed
to c
ance
r in
PH
OPD
T w
as s
igni
fican
tly lo
wer
tha
n in
O
M (
p =
0.02
7). T
here
was
no
sign
ifica
nt d
iffer
ence
in s
quam
ous
over
grow
th
betw
een
grou
ps w
hen
com
pare
d pe
r pa
tient
or
per
biop
sy o
r w
hen
the
aver
age
no. o
f bio
psie
s w
ith s
quam
ous
over
grow
th w
ere
com
pare
d pe
r pa
tient
. Sq
uam
ous
over
grow
th d
id n
ot o
bscu
re t
he m
ost
adva
nced
neo
plas
ia in
any
pa
tient
AE
s In
the
initi
al p
hase
of t
he t
rial
, the
mos
t co
mm
on A
Es w
ere
phot
osen
sitiv
ity (
69%
) an
d oe
soph
agea
l str
ictu
res
(36%
). A
ll ph
otos
ensi
tivity
ev
ents
wer
e re
solv
ed a
nd 9
4% o
f pat
ient
s w
ith s
tric
ture
s w
ere
stri
ctur
e fr
ee
duri
ng t
he c
ours
e of
the
initi
al p
hase
. Eve
nts
of s
ever
e in
tens
ity w
ere
sim
ilar
for
PHO
PDT
(16
%)
and
OM
(15
%)
with
65%
of t
he P
HO
PDT
gro
up b
eing
re
late
d to
the
tre
atm
ent
com
pare
d w
ith 2
% in
the
OM
gro
up. F
rom
yea
rs 2
to
5, t
here
wer
e no
SA
Es a
nd o
f tho
se A
Es r
epor
ted,
non
e w
as a
ttri
bute
d to
th
e tr
eatm
ents
. The
re w
ere
no p
hoto
sens
itivi
ty A
Es o
ccur
ring
dur
ing
the
long
te
rm p
hase
. Ful
l det
ails
of a
ll A
ES, b
oth
rela
ted
and
unre
late
d to
tre
atm
ent
are
avai
labl
e in
the
pap
erR
esou
rce
use
Not
ass
esse
d
Aut
hors
’ con
clus
ions
T
his
tria
l sho
ws
that
PD
T w
ith P
hoto
frin
is a
cl
inic
ally
and
sta
tistic
ally
ef
fect
ive
ther
apy
in
prod
ucin
g lo
ng-t
erm
ab
latio
n of
HG
D a
nd
redu
cing
the
pot
entia
l im
pact
of c
ance
r co
mpa
red
with
OM
Bri
ef s
tudy
app
rais
al
Thi
s w
as a
RC
T w
ith
proc
edur
es fo
r bl
indi
ng
of o
utco
me
asse
ssor
s. O
utco
mes
wer
e de
fined
an
d ap
prop
riat
ely
asse
ssed
and
AEs
no
ted.
Lon
ger-
term
FU
w
as u
sed
to t
race
the
de
velo
pmen
t of
dys
plas
ia
and
prog
ress
ion
to
canc
er. T
he r
esul
ts o
f th
is t
rial
app
ear
to b
e re
liabl
e w
ith t
he c
avea
t be
ing
the
larg
e nu
mbe
r of
rec
ruiti
ng c
entr
es
(and
ver
y sm
all n
umbe
rs
of p
atie
nts
at s
ome
site
s) w
hich
may
hav
e re
sulte
d in
bet
wee
n-si
te d
iffer
ence
s, su
ch
as t
he d
eliv
ery
of t
he
inte
rven
tion
(e.g
. var
ying
ex
pert
ise
in d
eliv
erin
g PD
T),
whi
ch m
ay h
ave
affe
cted
the
ove
rall
resu
lts. T
he n
umbe
r re
crui
ted
at in
divi
dual
si
tes
rang
ed fr
om o
ne t
o 51
par
ticip
ants
OM
, om
epra
zole
; PH
OPD
T, Ph
otof
rin
and
omep
razo
le.
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
249Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
R
agun
ath
et a
l. (2
005)
100
Link
ed
publ
icat
ions
210
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry U
KLa
ngua
ge E
nglis
hSt
udy
desi
gn
RC
TN
o. o
f pa
rtic
ipan
tsTo
tal:
26In
terv
entio
n: P
DT:
13 C
ompa
rato
r: A
PC:
13 No.
of r
ecru
itin
g ce
ntre
s N
ot
stat
edFo
llow
-up
peri
od a
nd
freq
uenc
y 4
mth
an
d 12
mth
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y BO
with
LG
D o
r H
GD
Mai
n el
igib
ility
cri
teri
a Pa
tient
s w
ith B
O ≥
3 cm
and
LG
D o
r H
GD
w
ith h
isto
logi
cal d
iagn
osis
con
firm
ed
on b
iops
y no
mor
e th
an 3
mth
be
fore
stu
dy e
ntry
wer
e el
igib
le. T
he
follo
win
g w
ere
excl
uded
: pat
ient
s w
ith o
esop
hage
al m
alig
nanc
y of
an
y fo
rm, p
revi
ous
oeso
phag
eal
rese
ctio
n, p
revi
ous
muc
osal
ab
lativ
e th
erap
y or
end
osco
pic
muc
osal
res
ectio
n, p
atie
nts
with
pr
edom
inan
tly t
ongu
es r
athe
r th
an
circ
umfe
rent
ial B
arre
tt’s
oeso
phag
us,
patie
nts
with
por
phyr
ia o
r pa
tient
s in
tole
rant
to
endo
scop
y. Pa
tient
s pr
egna
nt, t
ryin
g to
get
pre
gnan
t or
no
t us
ing
cont
race
ptio
n w
ere
also
ex
clud
edPa
tien
t ch
arac
teri
stic
s%
Mal
e: 81
Med
ian
age:
60 yr
Age
ran
ge: 3
5–86
yrM
edia
n BO
leng
th: 4
cmD
yspl
asia
: HG
D, 3
(12%
), 23
(88%
)C
onco
mit
ant
trea
tmen
t A
fter
the
proc
edur
es, p
atie
nts
rece
ived
a
high
-dos
e PP
I, la
nsop
razo
le 6
0 m
g/d,
du
ring
the
tre
atm
ent
peri
od a
nd
wer
e th
en m
aint
aine
d on
30
mg/
d.
All
patie
nts
also
rec
eive
d tw
o ta
blet
s of
co-
coda
mol
, to
be t
aken
ev
ery
6 hr
as
pain
rel
ief f
or 2
4–48
hr
afte
r th
e tr
eatm
ent.
A fe
w p
atie
nts
also
rec
eive
d 1
g of
suc
ralfa
te e
very
6
hr fo
r re
tros
tern
al d
isco
mfo
rt a
nd
tran
sien
t dy
spha
gia
Tria
l tre
atm
ents
PD
T w
ith P
hoto
frin
vs A
PCIn
terv
enti
on 2
mg/
kg o
f Pho
tofr
in w
as in
ject
ed
intr
aven
ously
48
hr b
efor
e ill
umin
atio
n w
ith la
ser.
PDT
was
per
form
ed u
sing
630
-nm
red
lase
r lig
ht w
ith a
pow
er o
utpu
t of
840
mW
del
iver
ing
200
J/cm
thr
ough
an
endo
scop
ical
ly in
sert
ed
PDT
bal
loon
. End
osco
py w
as p
erfo
rmed
un
der
intr
aven
ous
seda
tion
with
mid
azol
am
5–15
mg
and
fent
anyl
50–
100 µ
g. In
trav
enou
s bu
scop
an w
as u
sed
as a
n an
timot
ility
age
nt.
A 3
-cm
win
dow
PD
T b
allo
on w
as in
sert
ed
over
a g
uide
wire
and
infla
ted
afte
r po
sitio
ning
, ad
jace
nt t
o th
e Ba
rret
t’s s
egm
ent.
The
lase
r fib
re
was
inse
rted
into
the
bal
loon
and
pos
ition
ed
to a
llow
uni
form
lase
r lig
ht d
istr
ibut
ion.
The
pr
oced
ure
was
rep
eate
d fo
r ev
ery
addi
tiona
l 3
cm o
f the
Bar
rett
’s se
gmen
t. Fu
rthe
r tr
eatm
ent
para
met
ers
wer
e de
scri
bed.
All
patie
nts
wer
e ad
mitt
ed t
o th
e ga
stro
ente
rolo
gy w
ard
and
nurs
ed in
a s
emi-d
ark
room
. The
war
d nu
rsin
g st
aff a
nd t
he p
atie
nts
wer
e gi
ven
inst
ruct
ions
an
d an
info
rmat
ion
leafl
et a
bout
avo
idin
g di
rect
su
nlig
ht a
nd b
righ
t in
door
ligh
ts fo
r 4–
8 w
kC
ompa
rato
r APC
: End
osco
py w
as p
erfo
rmed
un
der
intr
aven
ous
seda
tion
with
mid
azol
am
5–15
mg.
Afte
r as
sess
men
t of
the
Bar
rett
’s se
gmen
t, A
PC w
as p
erfo
rmed
usi
ng t
he E
RBE
IC
C 2
00 A
rgon
Bea
mer
. APC
was
app
lied
until
a
whi
te c
oagu
lum
app
eare
d at
a p
ower
set
ting
of
65 W
and
arg
on g
as fl
ow o
f 1.8
l/m
in. D
epen
ding
on
the
leng
th o
f the
Bar
rett
’s se
gmen
t an
d pa
tient
tol
erab
ility
, APC
was
car
ried
out
in o
ne
or m
ore
sess
ions
with
an
inte
rval
of 2
–4 w
k be
twee
n th
e se
ssio
ns. T
he t
reat
men
t go
al
was
com
plet
e ab
latio
n of
BO
and
dys
plas
ia
or a
max
imum
of s
ix s
essi
ons
whe
n co
mpl
ete
abla
tion
was
not
ach
ieve
d. F
urth
er d
etai
ls w
ere
prov
ided
in t
he p
aper
Mor
talit
y N
ot a
sses
sed
Mor
bidi
tyM
edia
n le
ngth
of B
O e
radi
cate
d at
4-m
th
FU: P
DT
57%
(3
cm);
APC
65%
(3
cm)
Med
ian
leng
th o
f BO
era
dica
ted
at
12-m
th F
U: P
DT
60%
(3
cm);
APC
56%
(2
.5 cm
)D
yspl
asia
era
dica
tion
at 4
mth
: PD
T 7
7%;
APC
62%
(p =
0.0
3)D
yspl
asia
era
dica
tion
at 1
2 m
th: P
DT
77
%; A
PC 6
7% N
SD
evel
opm
ent
of m
alig
nanc
y at
12
mth
: PD
T o
ne; A
PC z
ero
AE
s Se
vere
AEs
:PD
T: fo
ur o
f 13
(31%
), ph
otos
ensi
tivity
tw
o; o
esop
hage
al s
tric
ture
tw
oA
PC: t
hree
of 1
3 (2
3%),
Oes
opha
geal
st
rict
ure,
tw
o; s
ever
e ch
est
pain
, od
ynop
hagi
a an
d fe
ver
requ
irin
g ho
spita
l ad
mis
sion
, one
Res
ourc
e us
e A
cos
t-ef
fect
iven
ess
anal
ysis
was
con
duct
ed fr
om t
he
pers
pect
ive
of t
he U
K N
HS.
The
cos
t of
PD
T p
er p
atie
nt w
as c
alcu
late
d at
£28
04
and
that
of A
PC £
1341
. The
ICER
s w
ere
calc
ulat
ed b
ased
on
diffe
renc
es in
cos
t an
d ef
fect
s be
twee
n th
e tw
o pr
oced
ures
fo
r BO
leng
th e
radi
catio
n an
d dy
spla
sia
erad
icat
ion
at 4
and
12
mth
. At
4 m
th
APC
was
the
dom
inan
t st
rate
gy b
eing
le
ss e
xpen
sive
and
mor
e ef
fect
ive.
At
12 m
th t
he in
crem
enta
l cos
t ra
tio w
as
£266
, i.e
. it
wou
ld c
ost
an a
dditi
onal
£2
66 fo
r ev
ery
perc
enta
ge r
educ
tion
in
Barr
ett’s
usi
ng P
DT.
Full
deta
ils o
f the
co
st-e
ffect
iven
ess
anal
ysis
are
pro
vide
d in
th
e pa
per
Aut
hors
’ con
clus
ions
PD
T a
nd A
PC a
re e
qual
ly
effe
ctiv
e in
era
dica
ting
Barr
ett’s
muc
osa.
How
ever
, PD
T is
mor
e ef
fect
ive
in e
radi
catin
g dy
spla
sia.
Long
-ter
m F
U is
nee
ded
to
asse
ss c
ance
r pr
even
tion
and
the
dura
bilit
y of
the
ne
osqu
amou
s ep
ithel
ium
. T
hese
inte
rven
tions
can
not
be r
ecom
men
ded
as y
et fo
r ro
utin
e pr
actic
eB
rief
stu
dy a
ppra
isal
T
his
was
a s
mal
l tri
al
that
will
like
ly h
ave
been
un
derp
ower
ed t
o de
tect
tr
eatm
ent
diffe
renc
es fo
r al
l out
com
es. T
his
wou
ld
also
hav
e im
pact
ed o
n th
e co
st e
ffect
iven
ess
anal
ysis
, w
hich
acc
ompa
nied
thi
s tr
ial. T
reat
men
t pr
otoc
ols
are
wel
l des
crib
ed b
ut
stud
y m
etho
ds s
uch
as p
roce
dure
s fo
r ra
ndom
isat
ion
and
blin
ding
ar
e le
ss w
ell d
escr
ibed
. The
au
thor
s ad
vise
a la
rger
tri
al
and
also
hig
hlig
ht t
he n
eed
for
long
er-t
erm
FU
Appendix 16
250
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
251
Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Zoe
pf e
t al.
(200
3)10
1
Dat
a so
urce
Abs
trac
tC
ount
ry G
erm
any
Lang
uage
Eng
lish
Stud
y de
sign
RC
TN
o. o
f par
tici
pant
sTo
tal:
20In
terv
entio
n: P
DT
10
Com
para
tor:
APC
10
No.
of r
ecru
itin
g ce
ntre
s N
ot s
tate
dFo
llow
-up
peri
od
and
freq
uenc
yPD
T: M
edia
n 27
mth
, ra
nge
12–4
2 m
thA
PC: M
edia
n 24
mth
, ra
nge
4–46
mth
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y Lo
ng-
segm
ent
BOM
ain
elig
ibili
ty
crit
eria
Not
sta
ted
Pati
ent
char
acte
rist
ics
% M
ale:
65M
edia
n ag
e: 68
yrA
ge r
ange
: 44–
77 yr
PDT:
4/1
0 LG
D, 6
/10
HG
DA
PC: 5
/10
LGD
, 5/1
0N
o dy
spla
sia
Con
com
itan
t tr
eatm
ent
Not
st
ated
Tria
l tre
atm
ents
PD
T v
s APC
Inte
rven
tion
PD
T: 6
0 m
g/kg
bw
of A
LA.
Cyl
indr
ical
diff
user
fibr
e in
the
cen
tre
of a
bal
loon
app
licat
or a
nd il
lum
inat
ed
usin
g a
diod
e la
ser
syst
em w
ith 1
50 J/
cm2 .
Num
ber
of t
reat
men
t se
ssio
ns w
as t
wo
(1–5
). Fu
rthe
r PD
T p
aram
eter
s w
ere
not
repo
rted
Com
para
tor A
PC: A
PC w
as a
pplie
d w
ith
a po
wer
of 7
0 W. T
he n
umbe
r of
tre
atm
ent
sess
ions
was
four
(2–
9)
Mor
talit
y N
ot a
sses
sed
Mor
bidi
ty R
educ
tion
of le
ngth
was
90%
fo
r PD
T (
rang
e 0–
100%
) an
d 90
% fo
r APC
(r
ange
50–
100%
)A
Es A
ll pa
tient
s w
ith P
DT
dev
elop
ed
naus
ea a
nd v
omiti
ng o
ver
a pe
riod
of
4 hr
afte
r tr
eatm
ent.
4/10
PD
T p
atie
nts
show
ed t
rans
ient
dys
phag
ia. N
o sk
in
phot
otox
ity w
as fo
und
afte
r PD
T. T
here
w
as n
o vo
miti
ng in
the
APC
gro
up
but
3/10
pat
ient
s de
velo
ped
tran
sien
t dy
spha
gia
and
one
med
iast
inal
em
phys
ema
and
trea
tmen
t ha
d to
be
inte
rrup
ted
Res
ourc
e us
e N
ot a
sses
sed
Aut
hors
’ con
clus
ions
Bot
h A
PC a
nd
PDT
can
abl
ate
BO b
ut fo
r APC
onl
y ha
lf as
man
y tr
eatm
ent
sess
ions
nee
ded
Bri
ef s
tudy
app
rais
al T
his
smal
l tri
al
was
rep
orte
d in
abs
trac
t on
ly a
nd n
o fu
rthe
r fu
ll pu
blic
atio
n w
as lo
cate
d. M
any
of t
he s
tudy
det
ails
and
met
hods
wer
e un
clea
r fr
om t
he a
bstr
act
and
the
qual
ity
of t
he t
rial
was
the
refo
re d
ifficu
lt to
as
sess
. Tre
atm
ent
grou
ps d
o no
t ap
pear
co
mpa
rabl
e in
ter
ms
of d
yspl
asia
bw, b
ody
wei
ght.
Appendix 16
250
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
251
Appendix 17 Oesophageal cancer data extraction
Appendix 17
252
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
253Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Can
to e
t al.
(200
5)10
7
Dat
a so
urce
Abs
trac
tC
ount
ry N
ot s
tate
dLa
ngua
ge E
nglis
hSt
udy
desi
gn N
on-
RC
TN
o. o
f par
tici
pant
sTo
tal:
80In
terv
entio
n: 5
8C
ompa
rato
r: 22
No.
of r
ecru
itin
g ce
ntre
s N
ot s
tate
d,
mul
ticen
tre
Follo
w-u
p pe
riod
an
d fr
eque
ncy
FU
at 4
–6 w
k, ev
ery
3 m
th
(yea
r 1)
, eve
ry 3
–6 m
th
(yea
r 2)
the
n ev
ery
6–12
mth
. EU
S an
d C
T s
cans
tak
en e
very
6
mth
(ye
ar 1
) th
en
ever
y 6–
12 m
th. M
ean
FU 3
1.2
mth
(6–
96)
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y T
1 oe
soph
agea
l can
cer
Mai
n el
igib
ility
cri
teri
a Pa
tient
s w
ith o
esop
hage
al S
CC
, ad
enoc
arci
nom
a of
the
oes
opha
gus,
EGJ s
tage
d as
T1
N0
M0
by E
US
or
CT
and
tha
t re
fuse
d, o
r w
ere
unfit
fo
r oe
soph
agec
tom
y, or
dec
lined
ra
diat
ion
ther
apy,
or d
eclin
ed
chem
orad
iatio
n th
erap
y w
ere
elig
ible
fo
r in
clus
ion
Pati
ent
char
acte
rist
ics
% M
ale:
70M
ean
age:
73 yr
Age
ran
ge: 4
3–91
yr; 7
4 Ba
rret
t’s
oeso
phag
eal c
arci
nom
as, t
wo
oeso
phag
eal s
quam
ous
cell
canc
ers,
four
oes
opha
goga
stri
c ju
nctio
n ad
enoc
arci
nom
asC
onco
mit
ant
trea
tmen
t N
ot
stat
ed
Tria
l tre
atm
ents
Bar
e fib
re P
s PD
T
alon
e vs
PD
T p
lus
EMR
Inte
rven
tion
PD
T a
lone
: Ps
infu
sion
(2
mg/
kg),
then
EG
D p
lus
PDT
(do
se
175–
300
J/cm
fibr
e, w
ith a
1.0
, 2.5
, 5
or 7
cm d
iffus
er fi
bre
with
out
a ba
lloon
cen
trin
g de
vice
)C
ompa
rato
r PD
T w
ith E
MR
: Le
sion
s w
ere
stag
ed a
nd r
emov
ed b
y EM
R b
efor
e PD
T fr
om 2
001
to 2
004
Mor
talit
y O
vera
ll an
d di
seas
e sp
ecifi
c 5-
yr s
urvi
val w
as 8
8% a
nd
100%
, res
pect
ivel
yM
orbi
dity
The
CR
rat
e w
as
89.7
% fo
r PD
T a
lone
vs
91.2
% fo
r PD
T +
EM
R (
p =
0.67
). N
ine
patie
nts
had
a 2n
d co
urse
for
abla
tion
of
HG
D o
r ca
ncer
. Fou
r pa
tient
s w
ith
new
HG
D in
res
idua
l Bar
rett
’s oe
soph
agea
l can
cers
of 9
–14
cm
wer
e tr
eate
d su
cces
sful
ly w
ith P
DT.
Five
(6.
2%)
subs
quam
ous
lesi
ons
diag
nose
d at
FU
with
HG
D/c
ance
r w
ere
trea
ted
succ
essf
ully
with
PD
T
(2),
chem
orad
iatio
n (1
) or
sur
gery
(2
)Q
oL a
nd r
etur
n to
nor
mal
ac
tivi
ty N
ot a
sses
sed
AE
s Si
x pa
tient
s (7
.5%
) re
quire
d ho
spita
lisat
ion
for
naus
ea, v
omiti
ng,
dehy
drat
ion,
tra
nsie
nt d
ysph
agia
, bl
eedi
ng o
r pa
in);
nine
(11
.2%
) de
velo
ped
PDT-
rela
ted
stri
ctur
es.
The
re w
ere
no t
reat
men
t-re
late
d de
aths
Res
ourc
e us
e N
ot a
sses
sed
Aut
hors
’ con
clus
ions
Ps-
PDT
w
ithou
t a
ballo
on c
entr
ing
devi
ce,
with
or
with
out
EMR
, is
a sa
fe a
nd
high
ly e
ffect
ive
cura
tive
trea
tmen
t fo
r ea
rly
canc
er o
f the
oes
opha
gus/
EGJ
Bri
ef s
tudy
app
rais
al T
his
stud
y w
as a
vaila
ble
only
as
a sh
ort
abst
ract
, the
met
hodo
logy
was
not
cl
earl
y re
port
ed a
nd it
was
unc
lear
w
hich
res
ults
wer
e ap
plic
able
to
each
tre
atm
ent
grou
p. A
s a
non-
rand
omis
ed s
tudy
, the
aut
hors
’ co
nclu
sion
s m
ay b
e ov
erly
str
ong
and
shou
ld b
e re
gard
ed w
ith c
autio
n
CT,
com
pute
rise
d to
mog
raph
y; EG
D, o
esop
hago
gast
rodu
oden
osco
py; E
GJ,
oeso
phag
ogas
tric
junc
tion;
EM
R, e
ndos
copi
c m
ucos
al r
esec
tion;
EU
S, en
dosc
opic
ultr
asou
nd s
can;
HG
D,
high
-gra
de d
yspl
asia
; Ps,
porfi
mer
sod
ium
.
Appendix 17
252
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
253
Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
G
rosj
ean
et a
l. (1
998)
108
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry
Switz
erla
ndLa
ngua
ge E
nglis
hSt
udy
desi
gn
Non
-RC
TN
o. o
f pa
rtic
ipan
tsTo
tal:
15 (
22
tum
ours
)In
terv
entio
n: 1
3 tu
mou
rs (
630
nm
PDT
)C
ompa
rato
r: N
ine
tum
ours
(51
4 nm
PD
T)
No.
of r
ecru
itin
g ce
ntre
s N
ot
stat
edFo
llow
-up
peri
od a
nd
freq
uenc
y FU
at
7–10
d, t
hen
3 m
th
afte
r tr
eatm
ent
and
twic
e pe
r ye
ar
ther
eafte
r
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y Su
perfi
cial
oe
soph
agea
l and
br
onch
ial c
ance
rsM
ain
elig
ibili
ty
crit
eria
It a
ppea
red
that
men
and
wom
en
with
one
or
seve
ral
biop
sy-p
rove
n su
perfi
cial
SC
C
of t
he b
ronc
hi o
r oe
soph
agus
Pati
ent
char
acte
rist
ics
% M
ale:
80A
ge r
ange
: 46–
79 yr
Mea
n A
ge: 5
9.8
yrA
ll pa
tient
s ha
d pr
evio
usly
rec
eive
d ra
diot
hera
py a
nd/o
r su
rger
y fo
r pr
imar
y in
vasi
ve c
ance
r of
the
he
ad a
nd n
eck
Con
com
itan
t tr
eatm
ent
Not
st
ated
Tria
l tre
atm
ents
PD
T a
t 63
0 nm
with
Ph
otof
rin
II vs
PD
T a
t 51
4 nm
with
Ph
otof
rin
IIIn
terv
enti
on P
DT
with
Pho
tofr
in
(630
nm
): A
fter
inje
ctio
n w
ith P
hoto
frin
II
(1 o
r 2
mg/
kg)
irra
diat
ion
with
630
nm
, 10
0 m
W/c
m2 (
tota
l dos
e 10
0 J/c
m2 )
arg
on
ion
pum
ped-
dye
lase
r un
der
gene
ral
anae
sthe
tic. M
icro
lens
and
/or
cylin
dric
al
light
dis
trib
utor
s w
ere
used
in t
he b
ronc
hi
and
180
or 2
40°
win
dow
ed c
ylin
dric
al li
ght
dist
ribu
tors
in t
he o
esop
hagu
s. Te
n tu
mou
rs
had
a dr
ug–l
ight
inte
rval
of 7
2 hr
, thr
ee
tum
ours
had
a d
rug–
light
inte
rval
of 1
hr.
If th
ere
was
less
tha
n C
R a
t 3-
mth
end
osco
py,
PDT
was
rep
eate
d. P
atie
nts
wer
e ad
vise
d to
av
oid
dire
ct s
unlig
ht fo
r 4–
6 w
k af
ter
drug
ad
min
istr
atio
nC
ompa
rato
r PD
T a
t 51
4 nm
: As
for
PDT
at
630
nm b
ut u
sing
514
nm
and
five
tu
mou
rs h
ad a
dru
g–lig
ht in
terv
al o
f 72
h,
four
tum
ours
had
a d
rug–
light
inte
rval
of
1 hr
Mor
talit
y N
ot a
sses
sed
Mor
bidi
ty C
R w
as s
een
in 9
/13
of t
he
supe
rfici
al t
umou
rs (
69%
) w
ith 6
30-n
m P
DT
vs
6/9
tum
ours
(67
%)
with
514
-nm
PD
T. In
the
630
-nm
PD
T g
roup
thr
ee t
umou
rs
show
ed a
PR
(vs
thr
ee in
524
-nm
gro
up)
and
one
tum
our
only
min
imal
ly r
educ
ed in
si
ze. I
n th
e oe
soph
agus
, bot
h w
avel
engt
hs
wer
e ef
fect
ive
in e
radi
catin
g in
situ
and
in
tram
ucos
al c
ance
r bu
t di
d bo
th c
ure
mor
e th
an h
alf o
f the
sub
muc
osal
tum
ours
. 2/1
0 tu
mou
rs t
reat
ed a
t a
drug
–lig
ht in
terv
al o
f 1
hr a
chie
ved
a C
RQ
oL a
nd r
etur
n to
nor
mal
act
ivit
y N
ot
asse
ssed
AE
s N
o m
ajor
com
plic
atio
ns w
ere
obse
rved
in e
ither
tre
atm
ent
grou
p. T
hree
63
0-nm
PD
T p
atie
nts
repo
rted
che
st p
ains
w
ith a
ssoc
iate
d hi
gh-g
rade
feve
r fo
r 10
d
afte
r PD
T (
two
with
ple
ural
effu
sion
, the
3r
d w
ith e
ndos
copi
c ev
iden
ce o
f oed
ema
and
eryt
hem
a on
the
pos
teri
or w
all o
f the
tr
ache
a at
the
leve
l of t
he o
esop
hage
al
canc
er).
All
thre
e pa
tient
s re
cove
red
with
an
timic
robi
al t
hera
pyR
esou
rce
use
Not
ass
esse
d
Aut
hors
’ con
clus
ions
PD
T w
ith 5
14-n
m
light
has
the
pot
entia
l to
cure
sup
erfic
ial
canc
er in
the
oes
opha
gus
and
bron
chi w
ith
the
sam
e pr
obab
ility
as
630-
nm P
DT.
In
the
oeso
phag
us, g
reen
ligh
t pr
even
ts d
eep
tissu
e da
mag
e, t
hus
redu
cing
the
ris
k of
pe
rfor
atio
nB
rief
stu
dy a
ppra
isal
The
num
bers
in
clud
ed in
thi
s st
udy
wer
e sm
all a
nd t
he
met
hods
wer
e no
t cl
earl
y re
port
ed –
pa
rtic
ular
ly in
ter
ms
of c
ompa
rabi
lity
of
the
two
grou
ps. T
he c
oncl
usio
ns m
ay n
ot
ther
efor
e be
rel
iabl
e. N
ote:
The
maj
ority
of
pat
ient
s in
thi
s tr
ial h
ad o
esop
hage
al
tum
ours
(14
/22)
, the
refo
re t
he r
esul
ts h
ave
been
incl
uded
in t
he o
esop
hage
al c
ance
r gr
oup
Appendix 17
254
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
255Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Hei
er e
t al
. (19
95)11
4
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry U
SALa
ngua
ge E
nglis
hSt
udy
desi
gn
RC
TN
o. o
f pa
rtic
ipan
tsTo
tal:
42In
terv
entio
n: 2
2C
ompa
rato
r: 20
No.
of r
ecru
itin
g ce
ntre
s N
ot
stat
edFo
llow
-up
peri
od
and
freq
uenc
y FU
at
1 w
k, th
en o
nce
per
mon
th. C
T
ever
y 3
mth
Trea
tmen
t in
tent
ion
Palli
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y O
esop
hage
al c
ance
rM
ain
elig
ibili
ty c
rite
ria
Patie
nts
with
dys
phag
ia c
ause
d by
bio
psy-
prov
en o
esop
hage
al m
alig
nanc
y th
at
wer
e no
t su
itabl
e fo
r, ha
d re
fuse
d or
faile
d su
rger
y, ra
diot
hera
py
and
chem
othe
rapy
wer
e el
igib
le
for
incl
usio
n. P
rior
the
rapy
had
to
have
end
ed a
t le
ast
1 m
th b
efor
e en
rolm
ent.
Excl
usio
n cr
iteri
a w
ere:
trac
heal
invo
lvem
ent
by
bron
chos
copy
and
Kar
nofs
ky
perf
orm
ance
sta
tus
< 30
Pati
ent
char
acte
rist
ics
% M
ale:
62A
ge r
ange
: 42–
87 yr
Mea
n ag
e: 70
yr (P
DT
) 73y
r N
d:YA
GM
ean
Kar
nofs
ky s
tatu
s fo
r bo
th
grou
ps w
as a
roun
d 73
–74
Ove
rall,
60%
of t
umou
rs w
ere
squa
mou
s an
d 40
% w
ere
aden
ocar
cino
ma.
Mos
t pa
tient
s ha
d so
me
kind
of p
rior
the
rapy
Con
com
itan
t tr
eatm
ent
Not
st
ated
Tria
l tre
atm
ents
PD
T w
ith D
HE
vs N
d:YA
G la
ser
Inte
rven
tion
PD
T: I
V D
HE
was
gi
ven
(2 m
g/kg
bw
), th
en il
lum
inat
ion
with
an
argo
n pu
mpe
d-dy
e la
ser.
630
± 2
nm (
300
J/cm
) re
d lig
ht w
as
deliv
ered
by
cylin
der-
diffu
sing
fibr
es,
and
tum
our
segm
ents
wer
e tr
eate
d se
quen
tially
in a
ret
rogr
ade
fash
ion.
Po
wer
den
sity
was
400
mW
/cm
fib
re t
ip. T
issu
e do
se w
as c
alcu
late
d fr
om li
ght
dose
del
iver
ed a
nd
surf
ace
area
exp
osed
, est
imat
ed
from
seg
men
tal l
umin
al d
iam
eter
. A
2nd
dose
cou
ld b
e gi
ven
if ne
cess
ary
(13
patie
nts)
. Pat
ient
s ad
vise
d to
re
stri
ct s
un e
xpos
ure
for
at le
ast
30 d
pos
t in
ject
ion.
If t
here
was
a
recu
rren
ce o
f tum
our
obst
ruct
ion
anot
her
cour
se o
f PD
T w
as g
iven
if
1 m
th h
ad e
laps
ed s
ince
DH
E in
ject
ion
Com
para
tor
Nd:
YAG
: Sta
ndar
d te
chni
que
was
use
d at
90 W
in a
re
trog
rade
fash
ion.
Las
er p
ulse
s w
ere
deliv
ered
thr
ough
qua
rtz
fibre
s (b
are
or c
oaxi
al a
ir fl
ow).
The
rapy
was
del
iver
ed e
very
2–4
d
until
lum
inal
pat
ency
was
ach
ieve
d.
Mos
t pa
tient
s re
quire
d tw
o se
ssio
ns
Mor
talit
y M
ean
surv
ival
was
not
si
gnifi
cant
ly d
iffer
ent
betw
een
PDT
and
Nd:
YAG
(14
5 vs
128
d,
p =
0.41
9)M
orbi
dity
At
1 m
th P
DT
was
as
soci
ated
with
a g
reat
er in
crea
se
in d
ieta
ry p
erfo
rman
ce (
p =
0.00
6),
Kar
nofs
ky p
erfo
rman
ce s
tatu
s (p
< 0
.001
) an
d oe
soph
agea
l gra
de
(p =
0.0
02)
com
pare
d w
ith N
d:YA
G.
Mea
n du
ratio
n of
res
pons
e w
ith
PDT
was
84
d vs
53
for
Nd:
YAG
, p
= 0.
008.
The
diff
eren
ce in
die
tary
le
vels
at
1 w
k an
d w
eigh
t ch
ange
be
twee
n tr
eatm
ent
grou
ps w
as n
s. C
R w
as s
een
in t
wo
PDT
pat
ient
s vs
one
QoL
and
ret
urn
to n
orm
al
acti
vity
Not
ass
esse
dA
Es
In t
he r
ando
mis
ed t
rial
pat
ient
s co
mpl
icat
ions
wer
e re
lativ
ely
few
: fist
ula
(one
PD
T p
atie
nt v
s tw
o), s
tric
ture
(ze
ro v
s tw
o), s
kin
phot
orea
ctio
n (fo
ur v
s ze
ro),
feve
r (fi
ve v
s on
e) a
nd lu
min
al p
lugg
ing
(five
vs
five)
Res
ourc
e us
e N
ot a
sses
sed
Aut
hors
’ con
clus
ions
PD
T c
an r
elie
ve
oeso
phag
eal o
bstr
uctio
n fr
om s
quam
ous
cell
and
aden
ocar
cino
ma
and
is a
n al
tern
ativ
e to
Nd:
YAG
the
rmal
nec
rosi
s w
ith a
long
er d
urat
ion
of r
espo
nse.
H
owev
er, P
DT
req
uire
s pa
tient
pre
caut
ions
to
min
imis
e sk
in p
hoto
reac
tions
Bri
ef s
tudy
app
rais
al T
his
was
a s
mal
l bu
t w
ell-c
ondu
cted
and
rep
orte
d st
udy
desp
ite t
he a
ppar
ent
lack
of b
lindi
ng o
f ou
tcom
e as
sess
ors.
The
ana
lyse
s ad
just
ed
for
conf
ound
ing
vari
able
s, an
d th
e si
gnifi
cant
ben
efits
in fa
vour
of P
DT
cou
ld
be c
onsi
dere
d as
pro
mis
ing
DH
E, d
ihae
mat
opor
phyr
in e
ther
s; ns
, not
sig
nific
ant.
Appendix 17
254
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
255
Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Lec
leire
et a
l. (2
008)
111
Dat
a so
urce
Abs
trac
tC
ount
ry N
ot s
tate
dLa
ngua
ge E
nglis
hSt
udy
desi
gn N
on-R
CT
No.
of p
arti
cipa
nts
Tota
l: 35
(37
lesi
ons)
Inte
rven
tion:
21
(22
lesi
ons)
(p
rim
ary
inte
nt P
DT
)C
ompa
rato
r: 14
(15
le
sion
s) (
PDT
indi
cate
d af
ter
loca
l fai
lure
of C
RT)
No.
of r
ecru
itin
g ce
ntre
s N
ot s
tate
dFo
llow
-up
peri
od a
nd
freq
uenc
y M
edia
n FU
15
mth
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y Ea
rly
stag
e oe
soph
agea
l ca
ncer
Mai
n el
igib
ility
cr
iter
ia N
ot s
tate
dPa
tien
t ch
arac
teri
stic
s N
ot r
epor
ted
in
deta
il, pa
per
stat
es n
o si
gnifi
cant
diff
eren
ces
betw
een
grou
ps.
Med
ian
tum
our
leng
th 2
cmC
onco
mit
ant
trea
tmen
t N
ot
stat
ed
Tria
l tre
atm
ents
PD
T in
pat
ient
s tr
eate
d in
pri
mar
y in
tent
vs
PDT
in
patie
nts
trea
ted
with
PD
T a
fter
loca
l fa
ilure
of d
efini
tive
CRT
Inte
rven
tion
Pri
mar
y in
tent
PD
T:
Afte
r IV
Pho
tofr
in (
2 m
g/kg
), ill
umin
atio
n w
ith a
dye
lase
r be
twee
n 48
h. T
he
mea
n nu
mbe
r of
PD
T s
essi
ons
was
1.
18. C
ontr
ol e
ndos
copi
es w
ith r
outin
e bi
opsi
es w
ere
plan
ned
6–8
wk
afte
r PD
T. N
o fu
rthe
r de
tails
wer
e re
port
edC
ompa
rato
r PD
T a
fter
faile
d C
RT: A
s fo
r pr
imar
y in
tent
PD
T e
xcep
t m
ean
num
ber
of P
DT
ses
sion
s w
as 1
.33
Mor
talit
y N
ot a
sses
sed
Mor
bidi
ty 1
6/22
lesi
ons
(73%
) w
ere
succ
essf
ully
tre
ated
in t
he p
rim
ary
inte
nt g
roup
vs
8/15
(53
%)
afte
r fa
iled
CRT
, p =
0.3
. The
re w
as n
o di
ffere
nce
in
recu
rren
ce r
ate
betw
een
grou
ps (
9 vs
14
%, n
s)Q
oL a
nd r
etur
n to
nor
mal
act
ivit
y N
ot a
sses
sed
AE
s Se
vere
com
plic
atio
ns w
ere
10%
in
the
prim
ary
inte
nt P
DT
gro
up v
s 50
%
for
faile
d C
RT (
p =
0.01
5) (
two
stri
ctur
es
requ
irin
g en
dosc
opic
dila
tion
vs t
wo
perf
orat
ions
and
five
str
ictu
res
requ
irin
g di
latio
n re
spec
tivel
y). D
eath
rat
e di
rect
ly
rela
ted
to P
DT
was
0%
in p
rim
ary
inte
nt
patie
nts
vs 1
4% fo
r fa
iled
CRT
(ns
)R
esou
rce
use
Not
ass
esse
d
Aut
hors
’ con
clus
ions
PD
T w
hen
indi
cate
d as
a s
alva
ge t
hera
py in
pa
tient
s w
ith lo
cal f
ailu
re a
fter
CRT
fo
r oe
soph
agea
l can
cer
tend
ed t
o be
le
ss e
ffect
ive
than
whe
n in
dica
ted
as
a 1s
t-lin
e tr
eatm
ent.
Mor
eove
r, se
vere
co
mpl
icat
ions
, inc
ludi
ng d
eath
-rel
ated
pr
oced
ures
wer
e si
gnifi
cant
ly m
ore
freq
uent
in p
atie
nts
trea
ted
afte
r pr
ior
CRT
Bri
ef s
tudy
app
rais
al F
ew
met
hodo
logi
cal a
nd p
atie
nt d
etai
ls w
ere
repo
rted
in t
his
abst
ract
of a
sm
all s
tudy
so
the
rel
iabi
lity
of t
he c
oncl
usio
ns is
un
clea
r. The
aut
hors
app
ear
to h
ave
draw
n co
nclu
sion
s at
odd
s w
ith t
he
stat
istic
al t
est
resu
ltsTh
e au
thor
s’ co
nclu
sions
do
not f
ollo
w fr
om
the
resu
lts re
port
ed
CRT
, che
mor
adio
ther
apy;
ns, n
ot s
igni
fican
t.
Appendix 17
256
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
257Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Li
ghtd
ale
et a
l. (1
995)
112
Dat
a so
urce
Fu
ll pu
blis
hed
pape
rC
ount
ry U
SALa
ngua
ge
Engl
ish
Stud
y de
sign
R
CT
No.
of
part
icip
ants
Tota
l: 23
6 (2
18
trea
ted)
Inte
rven
tion:
11
8 (1
10
trea
ted)
Com
para
tor:
118
(108
tr
eate
d)N
o. o
f re
crui
ting
ce
ntre
s 24
Follo
w-u
p pe
riod
and
fr
eque
ncy
FU
at 1
wk,
then
1,
2, 3
and
6 m
th
Trea
tmen
t in
tent
ion
Palli
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y O
esop
hage
al c
arci
nom
aM
ain
elig
ibili
ty c
rite
ria
Patie
nts
with
a b
iops
y-pr
oven
oes
opha
geal
m
alig
nanc
y an
d th
at w
ere
too
debi
litat
ed fo
r, re
fuse
d, fa
iled
to
resp
ond
to o
r ha
d a
recu
rren
ce
follo
win
g ch
emot
hera
py, r
adia
tion
ther
apy
or s
urge
ry w
ere
elig
ible
for
incl
usio
n. A
lso
patie
nts
with
SC
C
or a
deno
carc
inom
a, an
d th
at w
ere
sym
ptom
atic
, had
mal
igna
ncy-
caus
ed
dysp
hagi
a to
sol
id fo
ods
and
a K
arno
fsky
sta
tus
of a
t le
ast
30%
wer
e el
igib
le. P
rior
the
rapy
was
req
uire
d to
be
term
inat
ed a
t le
ast
4 w
k be
fore
ra
ndom
isat
ion.
Bro
ncho
scop
y w
as
requ
ired
for
tum
ours
at
or a
bove
th
e le
vel o
f the
car
ina.
Patie
nts
with
in
volv
emen
t of
the
tra
cheo
bron
chia
l tr
ee a
nd t
hose
tha
t ha
d pr
ior
trea
tmen
t fo
r oe
soph
agea
l car
cino
ma
with
PD
T o
r N
d:YA
G la
ser
wer
e ex
clud
ed. C
oncu
rren
t ra
diat
ion
and
chem
othe
rapy
wer
e no
t pe
rmitt
edPa
tien
t ch
arac
teri
stic
s%
Mal
e: 72
Med
ian
age:
PDT
68
yr; N
d:YA
G 7
2 yr
Med
ian
Kar
nofs
ky p
erfo
rman
ce s
tatu
s: 80
%Pr
ior
ther
apy:
45%
Med
ian
tum
our
leng
th: P
DT
6 cm
; N
d:YA
G 5
cmA
deno
carc
inom
a 51
%, t
he r
est
had
SCC
Con
com
itan
t tr
eatm
ent
Not
st
ated
Tria
l tre
atm
ents
PD
T v
s N
d:YA
G
lase
rIn
terv
enti
on P
DT:
40–
50 h
r af
ter
sing
le in
trav
enou
s in
ject
ion
with
Ps
(2
mg/
kg b
w),
illum
inat
ion
by
red
light
(63
0 nm
) pr
ovid
ed b
y a
cont
inuo
us w
ave
argo
n pu
mpe
d-dy
e la
ser
and
deliv
ered
via
an
optic
al
quar
tz fi
bre
with
a c
ylin
dric
al
diffu
sing
tip
(40
0 m
W/c
m, t
otal
dos
e 30
0 J/c
m).
Afte
r 2–
3 d
patie
nts
wer
e re
-end
osco
ped
to d
ebri
de t
he n
ecro
tic
tum
our
and
resi
dual
tum
our
coul
d be
tre
ated
with
a 2
nd a
pplic
atio
n of
la
ser
light
(sa
me
dose
). A
max
imum
of
thre
e co
urse
s at
1-m
th in
terv
als
was
pe
rmitt
edC
ompa
rato
r N
d:YA
G la
ser
ther
apy:
A la
ser
pow
er s
ettin
g of
15–
90 W
an
d pu
lse
dura
tion
of 0
.5–4
.0 s
was
us
ed (
deliv
ered
with
eith
er c
onta
ct
or n
on-c
onta
ct t
echn
ique
via
qua
rtz
fibre
s). E
ach
sess
ion
ende
d w
hen
the
endo
scop
ist
thou
ght
max
imum
ac
hiev
able
ben
efit
or m
axim
um p
atie
nt
tole
ranc
e w
as r
each
ed. R
epea
t se
ssio
ns
coul
d be
giv
en if
initi
al r
espo
nse
was
dee
med
insu
ffici
ent
(the
cou
rse
was
dee
med
com
plet
e w
hen
the
inve
stig
ator
bel
ieve
d dy
spha
gia
had
been
pal
liate
d or
furt
her
ther
apy
wou
ld b
e fu
tile)
Mor
talit
y N
ot a
sses
sed
Mor
bidi
ty D
ysph
agia
gra
des
sign
ifica
ntly
impr
oved
from
bas
elin
e at
1 w
k (P
DT
–0.
73 v
s N
d:YA
G
–0.9
0) a
nd 1
mth
(PD
T –
0.75
vs
Nd:
YAG
–0.
68)
with
bot
h tr
eatm
ents
(n
s di
ffere
nce
betw
een
trea
tmen
t gr
oups
). O
bjec
tive
tum
our
resp
onse
(r
espo
nder
s: pa
tient
s w
ith C
R o
r PR
) w
as 4
4% P
DT
vs
48%
Nd:
YAG
(ns
) at
1
wk
and
32%
PD
T v
s 20
% N
d:YA
G
at 1
mth
(p
< 0.
05).
Dat
a w
as o
btai
ned
from
80%
pat
ient
s at
1 w
k an
d 60
%
at 1
mth
. Sub
grou
p an
alys
es s
how
ed
ns d
iffer
ence
s be
twee
n gr
oups
but
th
ere
was
a t
rend
in fa
vour
of P
DT
fo
r ob
ject
ive
tum
our
resp
onse
rat
es
in t
he u
pper
and
low
er t
hird
of t
he
oeso
phag
us, t
umou
rs >
10
cm a
nd in
pa
tient
s th
at r
ecei
ved
prio
r th
erap
y. T
here
was
no
diffe
renc
e be
twee
n gr
oups
for
patie
nts
with
squ
amou
s ce
ll ca
ncer
and
ade
noca
rcin
oma
QoL
and
ret
urn
to n
orm
al a
ctiv
ity
Not
ass
esse
dA
Es
Sign
ifica
ntly
mor
e PD
T p
atie
nts
had
an A
E (9
2% v
s 82
%, p
< 0
.05)
. Su
nbur
n (1
9% P
DT
vs
0%),
naus
ea (
8%
vs 2
%),
feve
r (1
6% v
s 5%
) an
d pl
eura
l ef
fusi
on (
10%
vs
2%)
wer
e si
gnifi
cant
ly
grea
ter
for
PDT
and
oes
opha
geal
pe
rfor
atio
n gr
eate
r fo
r N
d:YA
G (
1%
vs 7
%) p
< 0
.05)
. All
PDT
pat
ient
s w
ere
phot
osen
sitiv
e fo
r 1–
2 m
th, n
one
seve
re. T
reat
men
t-re
late
d re
spir
ator
y in
suffi
cien
cy o
ccur
red
in 3
% P
DT
(vs
1%
). Se
vere
AEs
wer
e eq
ual o
vera
ll fo
r bo
th t
reat
men
tsR
esou
rce
use
Not
ass
esse
d
Aut
hors
’ con
clus
ions
PD
T w
ith
porfi
mer
sol
utio
n ha
s ov
eral
l equ
al
effic
acy
to N
d:YA
G la
ser
ther
mal
ab
latio
n fo
r pa
lliat
ion
of d
ysph
agia
in
oes
opha
geal
can
cer,
and
equa
l or
bett
er o
bjec
tive
tum
our
resp
onse
ra
te. T
empo
rary
pho
tose
nsiti
vity
is a
lim
itatio
n, b
ut P
DT
is c
arri
ed o
ut w
ith
grea
ter
ease
and
is a
ssoc
iate
d w
ith
few
er a
cute
per
fora
tions
tha
n N
d:YA
G
lase
r th
erap
yB
rief
stu
dy a
ppra
isal
The
met
hods
w
ere
gene
rally
wel
l-des
crib
ed t
houg
h a
few
feat
ures
wer
e no
t re
port
ed.
It m
ay h
ave
been
use
ful t
o ga
uge
patie
nt/in
vest
igat
or o
pini
on o
f eas
e of
tre
atm
ent
and
impo
rtan
ce o
f ph
otos
ensi
tivity
to
QoL
to
info
rm t
he
conc
lusi
ons
ns, n
ot s
igni
fican
t.
Appendix 17
256
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
257Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Mai
er e
t al.
(200
0)11
5
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry A
ustr
iaLa
ngua
ge E
nglis
hSt
udy
desi
gn N
on-
RC
TN
o. o
f par
tici
pant
sTo
tal:
52In
terv
entio
n: 2
3 (P
DT
)C
ompa
rato
r: 29
(PD
T
unde
r H
BO)
No.
of r
ecru
itin
g ce
ntre
s N
ot s
tate
dFo
llow
-up
peri
od
and
freq
uenc
y FU
at
1 m
th, t
hen
ever
y 3
mth
Trea
tmen
t in
tent
ion
Palli
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y A
dvan
ced
canc
er o
f the
upp
er
gast
roin
test
inal
tra
ctM
ain
elig
ibili
ty c
rite
ria
It ap
pear
ed
that
pat
ient
s w
ith a
dvan
ced
canc
er
of t
he u
pper
gas
troi
ntes
tinal
tra
ct
who
wer
e no
t el
igib
le fo
r re
sect
ion
trea
tmen
t du
e to
poo
r pe
rfor
man
ce
stat
us, f
unct
iona
l and
/or
anat
omic
in
oper
abili
ty, a
nd/o
r an
atom
ic
inop
erab
ility
, and
/or
refu
sing
sur
gery
w
ere
elig
ible
for
incl
usio
nPa
tien
t ch
arac
teri
stic
s%
Mal
e: 81
Age
ran
ge: 4
6–87
yrM
ean
age:
67.3
yrM
ost
patie
nts’
can
cers
wer
e ju
dged
to
be
stag
e III
, dys
phag
ia s
core
s va
ried
acr
oss
leve
ls 2
, 3 a
nd 4
and
no
sign
ifica
nt d
iffer
ence
s at
bas
elin
e w
ere
foun
d. T
umou
rs w
ere
SCC
in 2
5 ca
ses,
aden
ocar
cino
ma
in 2
5 ca
ses.
Furt
her
patie
nt c
hara
cter
istic
s w
ere
repo
rted
Con
com
itan
t tr
eatm
ent
Befo
re
PDT,
12 (
seve
n in
PD
T, fiv
e in
PD
T/
HBO
) pa
tient
s un
derw
ent
dila
tatio
n an
d re
trog
rade
Nd:
YAG
lase
r di
sobl
itera
tion
Tria
l tre
atm
ents
PD
T v
s PD
T
unde
r H
BOIn
terv
enti
on P
DT:
Pho
tosa
n-3
(2 m
g/kg
) w
as a
dmin
iste
red
intr
aven
ously
. Afte
r 48
hr,
PDT,
usin
g a
fibre
with
a 1
-cm
tip
rad
ial
light
-diff
usin
g cy
linde
r, w
as in
sert
ed
usin
g an
end
osco
pe. I
llum
inat
ion
dose
was
300
J/cm
of fi
bre,
630
nm
ap
plie
d by
a K
TP-
Nd:
YAG
lase
r. Tr
eatm
ent
was
und
er s
hort
-te
rm in
trav
enou
s an
aest
hesi
a. 2–
3 d
afte
r PD
T, en
dosc
opy
was
re
peat
ed, a
nd n
ecro
tic t
issu
e re
mov
ed m
echa
nica
lly if
nec
essa
ry.
Trea
tmen
t co
uld
be r
epea
ted
afte
r 3
mth
if n
eces
sary
but
mos
t pa
tient
s re
ceiv
ed o
ne s
essi
onC
ompa
rato
r PD
T u
nder
HBO
(P
DT
/HBO
): A
s fo
r PD
T b
ut
unde
r H
BO a
t a
leve
l of 2
ATA
in
a h
yper
bari
c ch
ambe
r. O
xyge
n w
as a
dmin
iste
red
with
the
Scu
ba
valv
e, t
rans
cuta
neou
s P o
2 lev
els
wer
e 50
0–75
0 m
mH
g. Be
fore
H
BO, p
atie
nts
had
an e
ar, n
ose
and
thro
at c
heck
-up
Mor
talit
y M
edia
n su
rviv
al a
fter
PDT
w
as 8
.7 m
th v
s 13
.8 m
th fo
r PD
T/
HBO
(p
= 0.
021)
Mor
bidi
ty A
t 3
mth
, dys
phag
ia s
core
ha
d de
crea
sed
in b
oth
grou
ps b
ut
ther
e w
as n
o si
gnifi
cant
diff
eren
ce
betw
een
trea
tmen
ts (
p =
0.43
). A
t 3
mth
, mea
n de
crea
se in
ste
nosi
s w
as
5.6
mm
in t
he P
DT
gro
up v
s 6.
3 m
m
PDT
/HBO
, p =
0.0
65. M
ean
decr
ease
in
tum
our
leng
th w
as 2
cm P
DT
vs
2.8
cm P
DT
/HBO
, p =
0.0
02Q
oL a
nd r
etur
n to
nor
mal
ac
tivi
ty A
sem
i-sol
id d
iet
was
po
ssib
le in
all
patie
nts
afte
r PD
T o
r PD
T/H
BOA
Es
No
maj
or c
ompl
icat
ions
rel
ated
to
PD
T, H
BO a
nd p
hoto
sens
itisa
tion,
an
d no
bar
otra
uma
of t
he e
ar o
r lu
ng o
r su
nbur
n w
as o
bser
ved.
M
inor
com
plic
atio
ns in
clud
ed:
post
inte
rven
tiona
l ody
noph
agia
(e
ight
PD
T v
s ni
ne P
DT
/HBO
), fe
ver
up t
o 39°
(five
vs
nine
) an
d ch
est
pain
for
1 or
2 d
(fiv
e vs
nin
e). S
ix
oeso
phag
otra
chea
l fist
ulas
wer
e fo
und
in t
wo
case
s (P
DT
at
5 an
d 17
mth
) an
d fo
ur c
ases
(PD
T/H
BO
at 4
, 7, 1
4 an
d 24
mth
). St
entin
g w
ith
coat
ed, s
elf-e
xpan
dabl
e st
ents
was
pe
rfor
med
in o
ne P
DT
pat
ient
at
16 m
th a
nd t
wo
PDT
/HBO
pat
ient
s at
14
and
17 m
th. O
ne p
atie
nt h
ad
haem
orrh
age
of t
he t
umou
r 18
mth
af
ter
PDT
/HBO
Res
ourc
e us
e N
ot a
sses
sed
Aut
hors
’ con
clus
ions
Com
bine
d PD
T/H
BO r
epre
sent
s a
new
app
roac
h in
the
tre
atm
ent
of o
esop
hage
al a
nd
card
ial c
ance
r, w
hich
app
ears
to
have
en
hanc
ed t
he e
ffica
cy o
f PD
TB
rief
stu
dy a
ppra
isal
Thi
s w
as a
sm
all p
ilot
stud
y th
at, d
espi
te n
ot
bein
g ra
ndom
ised
, doe
s se
em t
o ha
ve
achi
eved
rea
sona
ble
com
pari
son
grou
ps. T
he a
utho
rs c
omm
ent
that
ra
ndom
isat
ion
was
not
pos
sibl
e du
e to
the
var
iabl
e av
aila
bilit
y of
the
ox
ygen
cha
mbe
r. The
con
clus
ions
ar
e re
ason
able
but
the
stu
dy w
ould
ha
ve b
enefi
ted
from
blin
ded
outc
ome
asse
ssor
s
ATA
, atm
osph
ere
abso
lute
.
Appendix 17
258
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
259Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Mai
er e
t al.
(200
0)11
6
Link
ed p
ublic
atio
ns21
1
Dat
a so
urce
Ful
l pub
lishe
d pa
per
Cou
ntry
Aus
tria
Lang
uage
Eng
lish
Stud
y de
sign
Non
-RC
TN
o. o
f par
tici
pant
sTo
tal:
75In
terv
entio
n: 3
1C
ompa
rato
r: 44
No.
of r
ecru
itin
g ce
ntre
s O
neFo
llow
-up
peri
od a
nd
freq
uenc
y FU
afte
r 1
mth
, th
en e
very
3 m
th
Trea
tmen
t in
tent
ion
Not
st
ated
Type
(s)
of c
ance
r an
d hi
stol
ogy
Adv
ance
d oe
soph
agea
l car
cino
ma
Mai
n el
igib
ility
cri
teri
a Pa
tient
s th
at w
ere
not
elig
ible
fo
r re
sect
ion
trea
tmen
t du
e to
si
gnifi
cant
com
orbi
dity
wer
e in
clud
edPa
tien
t ch
arac
teri
stic
s%
Mal
e: 80
Mea
n ag
e: PD
T a
lone
, 67
yr;
PDT
/HBO
67.
5A
ge r
ange
: 46–
87 yr
Can
cer
stag
e: III
, 59;
IV, 1
6 D
ysph
agia
sc
ore:
leve
l 2, 2
3; le
vel 3
, 37
; lev
el 4
, 15.
40
SCC
, 35
aden
ocar
cino
ma
Furt
her
patie
nt c
hara
cter
istic
s w
ere
repo
rted
Con
com
itan
t tr
eatm
ent
Not
sta
ted
Tria
l tre
atm
ents
PD
T v
s PD
T/H
BOIn
terv
enti
on P
DT:
H
pD g
iven
intr
aven
ously
(2
mg/
kg)
and
cam
oufla
ge
skin
pro
tect
ion
used
for
2 w
k, th
en s
unbl
ock
for
10 w
k. PD
T g
iven
48
hr
afte
r se
nsiti
satio
n w
ith
a fib
re (
1-cm
tip
, rad
ial
light
diff
usin
g cy
linde
r)
inse
rted
thr
ough
the
bio
psy
chan
nel o
f the
end
osco
pe
(sev
eral
pla
cem
ents
wer
e ne
cess
ary)
. Lig
ht d
ose
was
30
0 J/c
m, 6
30 n
m a
pplie
d w
ith a
KT
P-N
d:YA
G la
ser
with
DY
E bo
x. T
reat
men
t gi
ven
unde
r sh
ort-
term
an
aest
hesi
a. En
dosc
opy
was
re
peat
ed 2
–3 d
afte
r PD
T
and
necr
otic
tis
sue
rem
oved
m
echa
nica
lly if
nec
essa
ry.
Prio
r to
PD
T, di
lata
tion
and
retr
ogra
de N
d:YA
G w
as
nece
ssar
y in
15
case
sC
ompa
rato
r PD
T/
HBO
: As
for
PDT
exc
ept
patie
nts
had
ear,
nose
an
d th
roat
che
ck-u
p, th
en
PDT
giv
en u
nder
HBO
(2
atm
osph
eres
) in
a w
alk-
in
hype
rbar
ic c
ham
ber
Mor
talit
y M
edia
n ov
eral
l sur
viva
l with
PD
T
was
7 m
th (
vs 1
2 m
th in
PD
T/H
BO g
roup
), p
= 0.
0098
. 12-
mth
sur
viva
l with
PD
T w
as
25%
vs
52%
with
PD
T/H
BOM
orbi
dity
At
3 m
th, s
teno
sis
decr
ease
d in
bo
th g
roup
s by
6 m
mIn
the
PD
T g
roup
med
ian
tum
our
leng
th
decr
ease
was
2 cm
vs
3 cm
in t
he P
DT
/HBO
gr
oup,
p =
0.00
02A
t 3-
mth
FU
(or
last
FU
in c
ase
of d
eath
)in
the
PD
T g
roup
dys
phag
ia s
core
cou
ld b
e lo
wer
ed b
y on
e le
vel i
n ei
ght
case
s (v
s ni
ne)
and
two
leve
ls in
23
case
s (v
s 33
) (a
nd in
th
e PD
T/H
BO g
roup
it c
ould
be
low
ered
by
thre
e le
vels
in t
wo
case
s); t
his
sign
ifica
ntly
fa
vour
ed P
DT
/HBO
(p
= 0.
0064
). N
o re
curr
ent
dysp
hagi
a w
as o
bser
ved
at 3
-mth
FU
for
eith
er g
roup
QoL
and
ret
urn
to n
orm
al a
ctiv
ity
At
leas
t a
sem
i-sol
id d
iet
was
pos
sibl
e in
all
patie
nts
afte
r ei
ther
tre
atm
ent
AE
s The
re w
ere
no m
ajor
pos
tinte
rven
tiona
l co
mpl
icat
ions
or
skin
pho
tose
nsiti
satio
n re
late
d to
eith
er t
reat
men
t. N
o ba
rotr
aum
a w
as o
bser
ved.
Min
or c
ompl
icat
ions
incl
uded
: od
ynop
hagi
a (P
DT
gro
up 6
vs
PDT
/HBO
8)
; fev
er u
p to
39°
in t
he a
ftern
oon
of t
he
inte
rven
tiona
l day
, one
in P
DT
vs
thre
e in
PD
T/H
BO);
ches
t pa
in fo
r 1
or 2
d (
four
in
PDT
vs
seve
n in
PD
T/H
BO).
30-d
ay m
orta
lity
was
0%
. Six
oes
opha
gotr
ache
al fi
stul
as in
tw
o pa
tient
s w
ere
foun
d (P
DT,
two
case
s; PD
T/
HBO
four
cas
es)
Res
ourc
e us
e H
ospi
talis
atio
n in
bot
h gr
oups
was
3–9
d (
med
ian
4.9
d)
Aut
hors
’ con
clus
ions
Com
bine
d PD
T/H
BO r
epre
sent
s a
new
ap
proa
ch in
the
tre
atm
ent
of
oeso
phag
eal a
nd c
ardi
al c
ance
r w
hich
app
ears
to
have
enh
ance
d th
e ef
ficie
ncy
of P
DT
Bri
ef s
tudy
app
rais
al T
his
stud
y w
as n
ot r
ando
mis
ed (
and
so m
ay h
ave
been
sub
ject
to
bias
) an
d in
clud
ed a
fair
ly s
mal
l nu
mbe
r of
pat
ient
s. T
he a
utho
rs
did
thou
gh a
ckno
wle
dge
that
de
finiti
ve c
oncl
usio
ns c
ould
not
be
draw
n ba
sed
on t
hese
res
ults
. Thi
s pu
blic
atio
n ap
pear
s to
be
the
sam
e st
udy
as a
rep
ort
of a
pilo
t st
udy
211 ,
alth
ough
the
aut
hors
wer
e no
t ex
plic
it ab
out
this
Appendix 17
258
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
259Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Mai
er e
t al.
(200
0)11
7
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry A
ustr
iaLa
ngua
ge E
nglis
hSt
udy
desi
gn N
on-
RC
TN
o. o
f par
tici
pant
sTo
tal:
119
Inte
rven
tion:
44
(PD
T a
nd
brac
hyra
diot
hera
py)
Com
para
tor:
75
(bra
chyr
adio
ther
apy)
No.
of r
ecru
itin
g ce
ntre
s N
ot s
tate
dFo
llow
-up
peri
od
and
freq
uenc
y FU
at
1 m
th, t
hen
ever
y 3
mth
Trea
tmen
t in
tent
ion
Palli
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y A
dvan
ced
oeso
phag
eal c
arci
nom
aM
ain
elig
ibili
ty c
rite
ria
Patie
nts
who
wer
e no
t el
igib
le fo
r re
sect
ion
due
to t
umou
r in
volv
emen
t of
th
e ad
jace
nt t
issu
e, p
oor
perf
orm
ance
sta
tus
plus
in
oper
able
sta
tus
as a
res
ult
of c
omor
bidi
ty, r
efus
al o
f su
rgic
al in
terv
entio
n, o
r a
com
bina
tion
of t
hese
, wer
e in
clud
edPa
tien
t ch
arac
teri
stic
s%
Mal
e: 81
Mea
n A
ge: M
en, 6
7 yr
; w
omen
65
yrA
ge R
ange
: 27–
93 yr
Can
cer
stag
e: III
, 80;
IV
, 39.
68
SCC
and
51
aden
ocar
cino
ma
Furt
her
patie
nt
char
acte
rist
ics
wer
e re
port
edC
onco
mit
ant
trea
tmen
t Pr
ior
to t
hera
py 2
1 pa
tient
s re
quire
d in
itial
dila
tatio
n an
d tu
mou
r ob
liter
atio
n w
ith N
d:YA
G
Tria
l tre
atm
ents
PD
T a
nd b
rach
ythe
rapy
vs
bra
chyt
hera
py a
lone
Inte
rven
tion
PD
T a
nd b
rach
ythe
rapy
: In
trav
enou
s ha
emat
opor
phyr
in w
as
adm
inis
tere
d (m
ean
1.5
inje
ctio
ns/p
atie
nt)
(2 m
g/kg
), af
ter
48 h
r PD
T t
reat
men
t us
ing
a fib
re w
ith 2
-cm
rad
ial l
ight
-diff
usin
g cy
linde
r in
sert
ed t
hrou
gh b
iops
y ch
anne
l of
an e
ndos
cope
(do
se 3
00 J/
cm fi
bre,
630
nm
ap
plie
d by
a K
TP-
Nd:
YAG
lase
r w
ith D
YE-
box)
. 2–3
d a
fter
PDT,
endo
scop
y re
peat
ed
and
necr
otic
tis
sue
rem
oved
. End
osco
py
was
per
form
ed a
fter
1 m
th, t
hen
ever
y 3
mth
. PD
T w
as n
ot r
epea
ted
with
in 3
mth
. Ir
idiu
m-1
92 b
rach
yrad
ioth
erap
y w
as g
iven
by
inse
rtio
n of
the
afte
rloa
ding
cat
hete
r. 5
Gy
per
sess
ion
was
giv
en, p
atie
nts
rece
ived
on
e to
four
ses
sion
s in
tot
al d
epen
ding
on
endo
scop
ic fi
ndin
gs a
nd d
ysph
agia
, with
3–
7 d
betw
een
sess
ions
. Thi
s pr
oces
s w
as
carr
ied
out
unde
r sh
ort-
term
intr
aven
ous
anae
sthe
sia,
com
bine
d w
ith t
opic
al
anae
sthe
sia
with
sup
port
ed b
reat
hing
. In
25
patie
nts
with
Kar
nofs
ky s
core
of >
80
(fair
co
nditi
on)
trea
tmen
t w
as c
ompl
eted
by
exte
rnal
bea
m ir
radi
atio
n us
ing
the
mul
tiple
fie
ld t
echn
ique
to
deliv
er m
ean
dose
of
44 G
yC
ompa
rato
r B
rach
ythe
rapy
: Iri
dium
-192
br
achy
radi
othe
rapy
was
giv
en b
y in
sert
ion
of t
he a
fterl
oadi
ng c
athe
ter.
5 G
y pe
r se
ssio
n w
as g
iven
, pat
ient
s re
ceiv
ed o
ne t
o fo
ur
sess
ions
in t
otal
dep
endi
ng o
n en
dosc
opic
fin
ding
s an
d dy
spha
gia,
with
3–7
d b
etw
een
sess
ions
. Thi
s pr
oces
s w
as d
one
unde
r sh
ort-
term
intr
aven
ous
anae
sthe
sia,
com
bine
d w
ith
topi
cal a
naes
thes
ia w
ith s
uppo
rted
bre
athi
ng.
In 1
7 pa
tient
s w
ith K
arno
fsky
sco
re o
f > 8
0 (fa
ir c
ondi
tion)
tre
atm
ent
was
com
plet
ed b
y ex
tern
al b
eam
irra
diat
ion
usin
g th
e m
ultip
le
field
tec
hniq
ue t
o de
liver
mea
n do
se o
f 44
Gy
Mor
talit
y M
ean
surv
ival
was
5.6
mth
for
brac
hyth
erap
y; 7.
7 m
th b
rach
ythe
rapy
and
ex
tern
al b
eam
irra
diat
ion;
6.3
mth
PD
T
brac
hyth
erap
y; 13
mth
PD
T, br
achy
ther
apy
and
exte
rnal
bea
m ir
radi
atio
n. T
here
was
a
sign
ifica
nt d
iffer
ence
with
PD
T*
(p =
0.0
129)
an
d ex
tern
al b
eam
irra
diat
ion*
(p
= 0.
0001
). T
his
was
bia
sed,
as
grou
ps w
ithou
t ex
tern
al
beam
irra
diat
ion
cont
aine
d pa
tient
s th
at
died
bef
ore
ente
ring
the
irra
diat
ion
regi
men
. (A
utho
rs’ c
omm
ent.)
*It
was
unc
lear
whi
ch p
atie
nt g
roup
s th
ese
resu
lts r
efer
red
toM
orbi
dity
Dys
phag
ia s
core
impr
oved
in
all
patie
nts
by o
ne t
o th
ree
leve
ls a
nd
was
sig
nific
antly
gre
ater
in t
he P
DT
gro
up
(p =
0.0
003)
. The
mea
n in
crea
se in
ope
ning
di
amet
er o
f tum
our-
rela
ted
sten
osis
was
si
gnifi
cant
ly g
reat
er in
the
PD
T g
roup
with
or
with
out
exte
rnal
bea
m ir
radi
atio
n th
an in
ei
ther
of t
he b
rach
ythe
rapy
con
ditio
nsQ
oL a
nd r
etur
n to
nor
mal
act
ivit
y T
here
wer
e no
sig
nific
ant
diffe
renc
es
betw
een
the
two
grou
ps in
ter
ms
of
Kar
nofs
ky p
erfo
rman
ce s
tatu
s sc
ores
at
3 m
th, p
= 0
.28
AE
s M
ajor
com
plic
atio
ns o
ccur
red
in 9
%
(11/
119)
of p
atie
nts,
incl
udin
g oe
soph
agea
l pe
rfor
atio
n af
ter
brac
hyth
erap
y, se
vere
ha
emor
rhag
ing
3 d
afte
r PD
T, sp
onta
neou
s pe
rfor
atio
n of
dis
tal o
esop
hagu
s w
ith
oeso
phag
omed
iast
inop
leur
al fi
stul
a an
d co
ncur
rent
ple
ural
em
phys
ema
5 m
th
afte
r PD
T, tr
ache
o-oe
soph
agea
l or
trac
heob
ronc
hial
fist
ula.
Due
to
stri
ctur
es,
dila
tion
was
nec
essa
ry a
fter
PDT
(fo
ur
patie
nts)
and
Nd:
YAG
(45
pat
ient
s). A
fter
PDT
28
patie
nts
repo
rted
ody
noph
agia
for
2–5
dR
esou
rce
use
Not
ass
esse
d
Aut
hors
’ con
clus
ions
PD
T h
as
been
sho
wn
to b
e an
effe
ctiv
e pa
lliat
ive
trea
tmen
t of
adv
ance
d oe
soph
agea
l can
cer.
How
ever
, pr
oper
pat
ient
sel
ectio
n is
ne
cess
ary
to p
reve
nt s
erio
us
com
plic
atio
nsB
rief
stu
dy a
ppra
isal
A
size
able
pro
port
ion
of p
atie
nts
in e
ach
grou
p w
ere
pre-
trea
ted
with
Nd:
YAG
, whi
ch d
id n
ot
appe
ar t
o be
acc
ount
ed fo
r in
th
e an
alys
is. T
his
tria
l app
ears
to
hav
e co
ntai
ned
four
sep
arat
e ar
ms,
alth
ough
thi
s w
as p
oorl
y de
scri
bed.
Pat
ient
s in
goo
d/fa
ir c
ondi
tion
rece
ived
a s
light
ly
diffe
rent
tre
atm
ent
prot
ocol
. T
hese
lim
itatio
ns m
ake
it di
fficu
lt to
eva
luat
e re
liabi
lity
of t
he
auth
ors’
con
clus
ions
Appendix 17
260
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
261Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Mai
er e
t al
. (20
01)11
8
Link
ed
publ
icat
ions
120
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry A
ustr
iaLa
ngua
ge E
nglis
hSt
udy
desi
gn
Non
-RC
TN
o. o
f pa
rtic
ipan
tsTo
tal:
49In
terv
entio
n: 2
2 (A
LA–P
DT
)C
ompa
rato
r: 27
(P
hoto
san-
PDT
)N
o. o
f rec
ruit
ing
cent
res
Not
st
ated
Follo
w-u
p pe
riod
an
d fr
eque
ncy
FU
at 1
mth
, the
n ev
ery
3 m
th
Trea
tmen
t in
tent
ion
Palli
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y A
dvan
ced
oeso
phag
eal c
ance
rM
ain
elig
ibili
ty
crit
eria
Pat
ient
s th
at
wer
e no
t el
igib
le fo
r re
sect
ion
trea
tmen
t du
e to
poo
r pe
rfor
man
ce
stat
us, f
unct
iona
l and
/or
anat
omic
al in
oper
abili
ty,
and/
or r
efus
ing
surg
ery
wer
e in
clud
edPa
tien
t ch
arac
teri
stic
s%
Mal
e: 78
Age
ran
ge: 4
6–88
yrM
ean
age:
ALA
, 69
yr;
Phot
osan
68
yrC
ance
r st
age:
III, 1
7; IV
32
. Dys
phag
ia s
core
va
ried
with
mos
t in
leve
l 2
or 3
but
no
sign
ifica
nt
diffe
renc
esO
vera
ll th
ere
wer
e 13
SC
C, 1
4 ad
enoc
arci
nom
aFu
rthe
r pa
tient
ch
arac
teri
stic
s w
ere
repo
rted
Con
com
itan
t tr
eatm
ent
Not
sta
ted
Tria
l tre
atm
ents
ALA
- PD
T v
s PD
T w
ith
Phot
osan
(H
pD).
Both
per
form
ed w
ith
addi
tiona
l hyp
erba
ric
oxyg
enat
ion
Inte
rven
tion
ALA
–PD
T: D
iagn
ostic
w
ork-
up w
as p
erfo
rmed
usi
ng b
ariu
m
oeso
phag
ogra
m, o
esop
hago
gast
rosc
opy,
bron
chos
copy
and
CT
sca
ns. O
ral
adm
inis
trat
ion
of A
LA (
60 m
g/kg
) th
en s
kin
prot
ectio
n by
cam
oufla
ge fo
r 24
hr.
6–8
hr
afte
r ALA
, PD
T w
as c
arri
ed o
ut u
sing
a fi
bre
with
2-c
m t
ip r
adia
l lig
ht-d
iffus
ing
cylin
der,
inse
rted
thr
ough
the
bio
psy
chan
nel o
f the
en
dosc
ope.
Lig
ht d
ose
was
300
J/cm
fibr
e an
d 63
0-nm
ligh
t w
as a
pplie
d by
KT
P-N
d:
YAG
lase
r ha
ving
a D
YE
mod
ule.
Add
ition
al
hype
rbar
ic o
xyge
natio
n w
as a
pplie
d (a
fter
an e
ar, n
ose
and
thro
at c
heck
-up)
at
leve
l 2 A
TA u
sing
a S
cuba
val
ve s
yste
m.
Trea
tmen
t w
as p
erfo
rmed
und
er s
hort
-ter
m
intr
aven
ous
anae
sthe
sia.
Endo
scop
y w
as
perf
orm
ed 2
–3 d
afte
r PD
T a
nd n
ecro
tic
tissu
e re
mov
ed. E
ndos
copy
was
the
n pe
rfor
med
afte
r 1
mth
, the
n ev
ery
3 m
th.
Incr
ease
d tu
mou
r le
ngth
and
dys
phag
ia a
t FU
indi
cate
d fu
rthe
r PD
T t
reat
men
t. N
o tr
eatm
ent
was
rep
eate
d w
ithin
3 m
th a
fter
the
1st
PDT
ses
sion
Com
para
tor
Phot
osan
-PD
T: A
s fo
r ALA
–PD
T e
xcep
t in
trav
enou
s ad
min
istr
atio
n of
Ph
otos
an (
2 m
g/kg
), 48
hr
befo
re P
DT
Mor
talit
y M
edia
n su
rviv
al fo
r A
LA g
roup
was
8 m
th v
s 9m
th,
p =
0.44
(K
apla
n–M
eier
sur
viva
l cu
rve
in p
aper
)M
orbi
dity
At
1 m
th, t
here
was
si
gnifi
cant
ly m
ore
impr
ovem
ent
in t
he A
LA g
roup
tha
n th
e Ph
otos
an g
roup
for
the
follo
win
g ou
tcom
es: d
ysph
agia
(p
= 0.
02),
tum
our
sten
osis
(p =
0.0
0000
) an
d tu
mou
r le
ngth
(p =
0.0
0001
4)Q
oL a
nd r
etur
n to
nor
mal
ac
tivi
ty K
arno
vsky
Per
form
ance
st
atus
impr
oved
by
23%
for
ALA
vs
44%
for
Phot
osan
, not
si
gnifi
cant
(p
= 0.
12)
AE
s N
o ba
rotr
aum
a of
th
e ea
r w
as o
bser
ved.
No
sunb
urn
occu
rred
in e
ither
gr
oup.
The
re w
ere
no m
ajor
A
Es. 3
0-da
y m
orta
lity
was
0%
. M
inor
com
plic
atio
ns w
ere:
post
inte
rven
tiona
l ody
noph
agia
(n
ine
in A
LA g
roup
vs
13);
feve
r up
to
39°
in t
he a
ftern
oon
of t
he
inte
rven
tiona
l day
(fiv
e vs
eig
ht);
ches
t pa
in fo
r 1
or 2
d (
nine
vs
13).
Afte
r ALA
adm
inis
trat
ion
all
patie
nts
expe
rien
ced
naus
eaR
esou
rce
use
Hos
pita
lisat
ion
was
4–6
d in
bot
h tr
eatm
ent
grou
ps
Aut
hors
’ con
clus
ions
Des
pite
the
lim
itatio
ns
of a
non
-ran
dom
ised
stu
dy, p
hoto
sens
itisa
tion
with
Pho
tosa
n se
ems
to b
e m
ore
effe
ctiv
e in
PD
T o
f adv
ance
d oe
soph
agea
l car
cino
ma
com
pare
d w
ith A
LAB
rief
stu
dy a
ppra
isal
The
con
clus
ions
tha
t co
uld
be d
raw
n w
ere
limite
d as
thi
s w
as a
sm
all,
non-
rand
omis
ed s
tudy
. Bas
elin
e ch
arac
teri
stic
s w
ere
larg
ely
sim
ilar
apar
t fr
om M
sta
ge a
nd t
he
auth
ors’
cau
tious
con
clus
ions
app
ear
relia
ble.
T
his
stud
y ap
pear
s to
hav
e be
en p
ublis
hed
twic
e (s
ee r
ef. 1
20)
with
Pho
tosa
n be
ing
desc
ribe
d as
HpD
. The
pat
ient
s, tr
eatm
ents
and
res
ults
ap
pear
to
be id
entic
al, t
here
fore
onl
y on
e st
udy
has
been
dat
a ex
trac
ted
ATA
, atm
osph
ere
abso
lute
.
Appendix 17
260
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
261Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Sav
ary
et a
l. (1
998)
109
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry S
witz
erla
ndLa
ngua
ge E
nglis
hSt
udy
desi
gn N
on-
RC
TN
o. o
f par
tici
pant
sTo
tal:
24 (
31 t
umou
rs)
Inte
rven
tion:
Nin
e tu
mou
rs (
HpD
-PD
T)
Com
para
tor:
Eigh
t tu
mou
rs (
Phot
ofri
n II-
PDT
)2n
d C
ompa
rato
r: Tw
o tu
mou
rs (
mT
HPC
-PD
T, 0.
15 m
g/kg
with
652
nm
)3r
d C
ompa
rato
r: O
ne
tum
our
(mT
HPC
-PD
T, 0.
3 m
g/kg
with
514
nm
)4t
h C
ompa
rato
r: 11
tu
mou
rs (
mT
HPC
-PD
T, 0.
15 m
g/kg
with
514
nm
)N
o. o
f rec
ruit
ing
cent
res
Not
sta
ted
Follo
w-u
p pe
riod
an
d fr
eque
ncy
FU a
t 10
d, 3
mth
, the
n 6-
mth
in
terv
als
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y Ea
rly
SCC
of t
he
oeso
phag
usM
ain
elig
ibili
ty
crit
eria
Bio
psy
confi
rmed
ear
ly
SCC
. Pat
ient
s w
ith
porp
hyri
a w
ere
excl
uded
Pati
ent
char
acte
rist
ics
% M
ale:
92A
ge r
ange
: 42–
79 yr
Mea
n ag
e: 56
yrTw
enty
-tw
o pa
tient
s ha
d a
hist
ory
of
prim
ary
inva
sive
hea
d an
d ne
ck c
ance
r, tw
o ha
d no
suc
h hi
stor
y. Tw
o pa
tient
s ha
d sy
nchr
onou
s tu
mou
rs,
five
patie
nts
deve
lope
d m
etac
hron
ous
earl
y ca
ncer
sC
onco
mit
ant
trea
tmen
t N
one
Tria
l tre
atm
ents
HpD
PD
T v
s Ph
otof
rin
II PD
T
vs m
TH
PC 0
.15
mg/
kg (
652
nm)
PDT
vs
mT
HPC
0.
3 m
g/kg
(51
4 nm
) PD
T v
s m
TH
PC 0
.15
mg/
kg
(514
nm
) PD
TIn
terv
enti
on H
pD P
DT:
Intr
aven
ous
HpD
w
as in
ject
ed (
3 m
g/kg
), th
en P
DT
giv
en w
ith a
n ar
gon
ion
pum
ped-
dye
lase
r af
ter
72 h
r (6
30 n
m,
100
J/cm
2 , 80
mW
/cm
2 ) fo
r 21
min
. Sur
face
ir
radi
atio
n us
ing
180
or 2
40°
win
dow
ed c
ylin
dric
al
light
dis
trib
utor
s (1
5 m
m d
iam
eter
) w
as u
sed
Com
para
tor
Phot
ofri
n II
PDT:
intr
aven
ous
Phot
ofri
n II
was
inje
cted
(1
or 2
mg/
kg),
then
PD
T g
iven
with
an
argo
n io
n pu
mpe
d-dy
e la
ser
afte
r 72
hr
[630
nm
(m
ost
patie
nts)
or
514n
m,
mea
n lig
ht d
ose
100
J/cm
2 , 90
mW
/cm
2 ] fo
r 19
min
. Su
rfac
e ir
radi
atio
n us
ing
180°
or
240°
win
dow
ed
cylin
dric
al li
ght
dist
ribu
tors
(15
-mm
dia
met
er)
was
use
d2n
d co
mpa
rato
r m
TH
PC 0
.15
mg/
kg (
652
nm)
PDT:
Intr
aven
ous
mT
HPC
was
inje
cted
(0
.15
mg/
kg),
then
PD
T g
iven
with
an
argo
n io
n pu
mpe
d-dy
e la
ser
afte
r 20
hr
(652
nm
, 6 o
r 8
J/cm
2 , 40
mW
/cm
2 ) fo
r 3
min
. Sur
face
irra
diat
ion
usin
g 18
0 or
240°
win
dow
ed c
ylin
dric
al li
ght
dist
ribu
tors
(15
-mm
dia
met
er)
wer
e us
ed3r
d co
mpa
rato
r m
TH
PC 0
.3 m
g/kg
(51
4 nm
) PD
T: in
trav
enou
s m
TH
PC w
as in
ject
ed
(0.3
mg/
kg),
then
PD
T g
iven
with
a a
rgon
ion
pum
ped-
dye
lase
r af
ter
20 h
r (5
14 n
m, 3
0 J/c
m2 ,
50 m
W/c
m2 )
for
10 m
in. S
urfa
ce ir
radi
atio
n us
ing
180
or 2
40 w
indo
wed
cyl
indr
ical
ligh
t di
stri
buto
rs
(15-
mm
dia
met
er)
was
use
d4t
h co
mpa
rato
r m
TH
PC 0
.15
mg/
kg (
514
nm)
PDT:
intr
aven
ous
mT
HPC
was
inje
cted
(0
.15
mg/
kg),
then
PD
T g
iven
with
an
argo
n io
n pu
mpe
d-dy
e la
ser
afte
r 20
or
96 h
r (5
14 n
m,
75 J/
cm2 ,
90 m
W/c
m2 )
for
14 m
in. S
urfa
ce
irra
diat
ion
usin
g 18
0 or
240°
win
dow
ed c
ylin
dric
al
light
dis
trib
utor
s (1
5-m
m d
iam
eter
) w
as u
sed
Mor
talit
y N
ot a
sses
sed
Mor
bidi
ty N
o tr
uly
sele
ctiv
e ne
cros
is w
as s
een
with
HpD
, Ph
otof
rin
II or
mT
HPC
whe
n ir
radi
atio
n w
as a
t 20
hr. W
ith
mT
HPC
(ir
radi
atio
n at
96
h) s
ome
patie
nts
had
necr
oses
tha
t w
ere
sele
ctiv
e. C
R r
ates
: HpD
= 8
9%,
mT
HPC
= 8
6%, P
hoto
frin
II =
75%
. Fa
ilure
s of
tre
atm
ent
acco
rdin
g to
sen
sitis
er u
sed
wer
e 1/
9 (1
1%)
in t
he H
pD g
roup
; 2/8
(2
5%)
Phot
ofri
n II
grou
p; 2
/14
(14%
) m
TH
PC g
roup
. Fai
lure
s of
tre
atm
ent
acco
rdin
g to
w
avel
engt
h us
ed w
ere
2/15
(13
%)
for
630
or 6
52 n
m; 3
/16
(19%
) fo
r 51
4 nm
QoL
and
ret
urn
to n
orm
al
acti
vity
Not
ass
esse
dA
Es A
ll pa
tient
s re
port
ed
burn
ing
sens
atio
n du
ring
the
in
ject
ion
of m
TH
PC. M
ajor
co
mpl
icat
ions
wer
e: St
enos
es
(tw
o), o
esop
hago
trac
heal
fist
ulas
in
PD
T p
atie
nts
(630
or
652
nm)
(tw
o, o
ne o
f whi
ch c
ompl
icat
ed
by o
esop
hage
al s
teno
sis)
. Thr
ee
patie
nts
that
did
not
follo
w
pres
crib
ed p
reca
utio
ns (
not
in
met
hods
) de
velo
ped
2nd-
degr
ee
sunb
urn
on t
he fa
ce a
nd h
ands
(o
ne H
pD p
atie
nt a
t 2
mth
; 2
0.15
mg/
kg m
TH
PC p
atie
nts
at
6 d) Res
ourc
e us
e N
ot a
sses
sed
Aut
hors
’ con
clus
ions
PD
T e
radi
cate
s ea
rly
SCC
s (T
1a a
nd T
1b)
of t
he
oeso
phag
us e
ffici
ently
. Tra
nsm
ural
ne
cros
es le
adin
g to
fist
ulas
can
be
avoi
ded
usin
g a
low
-pen
etra
ting
wav
elen
gth
of la
ser
light
(gr
een
light
at
514
.5 n
m in
stea
d of
red
ligh
t at
630
or
652
nm
). St
enos
es a
lway
s re
sult
from
circ
umfe
rent
ial i
rrad
iatio
n of
th
e oe
soph
agea
l wal
l, an
d th
is c
an
be a
void
ed b
y us
ing
a 18
0° o
r 24
0°
win
dow
ed c
ylin
dric
al li
ght
dist
ribu
tor
Bri
ef s
tudy
app
rais
al T
his
was
a
rela
tivel
y sm
all t
rial
with
mul
tiple
co
mpa
rato
r ar
ms,
the
met
hods
wer
e no
t cl
earl
y re
port
ed a
nd a
s th
e au
thor
s th
emse
lves
com
men
t –
the
smal
l sa
mpl
es p
recl
ude
any
firm
con
clus
ions
, so
the
res
ults
may
not
be
relia
ble
Appendix 17
262
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
263Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Sco
tinio
tis e
t al.
(200
0)11
0
Dat
a so
urce
Abs
trac
tC
ount
ry U
SALa
ngua
ge E
nglis
hSt
udy
desi
gn N
on-R
CT
No.
of p
arti
cipa
nts
Tota
l: 37
Inte
rven
tion:
12
(PD
T)
Com
para
tor:
Six
EMR
2nd
Com
para
tor:
19
(oes
opha
gect
omy)
No.
of r
ecru
itin
g ce
ntre
s N
ot s
tate
dFo
llow
-up
peri
od a
nd
freq
uenc
y M
ean
FU 1
5 m
th
(ran
ge 2
–28
mth
). PD
T a
nd
EMR
pat
ient
FU
4–6
wk
afte
r tr
eatm
ent,
then
eve
ry
3–6
mth
; oes
opha
gect
omy
patie
nt F
U d
icta
ted
by
sym
ptom
s
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y Su
perfi
cial
oes
opha
geal
ca
ncer
Mai
n el
igib
ility
cr
iter
ia S
uper
ficia
l oe
soph
agea
l can
cer
dete
rmin
ed b
y EU
S an
d C
T in
clud
ing
HG
D,
carc
inom
a in
situ
or
intr
amuc
osal
car
cino
ma
Pati
ent
char
acte
rist
ics
Mea
n ag
e: PD
T, 76
; EM
R, 7
3;
oeso
phag
ecto
my,
65T
hirt
y-si
x ad
enoc
arci
nom
as, o
ne
SCC
Con
com
itan
t tr
eatm
ent
Not
sta
ted
Tria
l tre
atm
ents
PD
T v
s EM
R v
s O
esop
hage
ctom
yIn
terv
enti
on P
DT:
No
deta
ils
repo
rted
Com
para
tor
EMR
: No
deta
ils
repo
rted
2nd
com
para
tor
Oes
opha
gect
omy:
No
deta
ils r
epor
ted
Mor
talit
y N
ot a
sses
sed
Mor
bidi
ty E
radi
catio
n of
lesi
ons
was
ac
hiev
ed in
9/1
2 (7
5%)
PDT,
5/6
(83%
) EM
R a
nd 1
8/19
(95
%)
oeso
phag
ecto
my
patie
nts
QoL
and
ret
urn
to n
orm
al a
ctiv
ity
Not
ass
esse
dA
Es
Stri
ctur
e oc
curr
ed in
6/1
2 (5
0%)
PDT,
0/6
EMR
and
10/
19
(53%
) oe
soph
agec
tom
y pa
tient
s. ≥
3 di
lata
tions
occ
urre
d in
4/1
2 (3
3%)
PDT,
0/6
EMR
and
7/1
9 (3
7%)
oeso
phag
ecto
my
patie
nts.
Oth
er
com
plic
atio
ns w
ere
repo
rted
for
smal
l nu
mbe
rs o
f pat
ient
sR
esou
rce
use
Not
ass
esse
d
Aut
hors
’ con
clus
ions
In p
oor
surg
ical
can
dida
tes
with
sup
erfic
ial
oeso
phag
eal c
arci
nom
a PD
T
and
EMR
ach
ieve
d ou
tcom
es
com
para
ble
to o
esop
hage
ctom
y in
go
od s
urgi
cal c
andi
date
s. PD
T a
nd
EMR
are
rea
sona
ble
alte
rnat
ives
to
oeso
phag
ecto
my
for
sele
cted
pat
ient
sB
rief
stu
dy a
ppra
isal
Thi
s sm
all
stud
y w
as a
vaila
ble
only
as
an a
bstr
act
and
few
met
hodo
logi
cal d
etai
ls w
ere
repo
rted
. The
stu
dy p
opul
atio
ns fo
r th
e di
ffere
nt in
terv
entio
ns d
id n
ot a
ppea
r to
be
com
para
ble
at b
asel
ine
with
PD
T/
EMR
pat
ient
s ch
osen
if s
ubop
timal
for
surg
ery.
In a
dditi
on n
o st
atis
tical
tes
ts
wer
e ca
rrie
d ou
t to
ver
ify t
he fi
ndin
gs,
the
resu
lts o
f thi
s st
udy
may
the
refo
re
not
be r
elia
ble
The
auth
ors’
conc
lusio
ns d
o no
t fol
low
fro
m th
e re
sults
repo
rted
EMR
, end
osco
pic
muc
osal
res
ectio
n.
Appendix 17
262
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
263Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Zha
ng e
t al.
(200
3)11
9
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry C
hina
Lang
uage
Chi
nese
Stud
y de
sign
RC
TN
o. o
f par
tici
pant
sTo
tal:
60In
terv
entio
n: 3
0C
ompa
rato
r: 30
No.
of r
ecru
itin
g ce
ntre
s O
ne h
ospi
tal
(out
patie
nts)
Follo
w-u
p pe
riod
an
d fr
eque
ncy
FU a
t 5
and
10 yr
Trea
tmen
t in
tent
ion
Palli
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y A
dvan
ced
oeso
phag
eal c
ance
rM
ain
elig
ibili
ty c
rite
ria
Dia
gnos
ed w
ith a
dvan
ced
oeso
phag
eal c
ance
r, su
itabl
e fo
r tr
eatm
ent
Pati
ent
char
acte
rist
ics
Age
: und
er 7
0 yr
Can
cer
leng
th: 5
–10
cm. N
o m
etas
tase
sC
onco
mit
ant
trea
tmen
t N
ot s
tate
d
Tria
l tre
atm
ents
PD
T w
ith
radi
othe
rapy
vs
radi
othe
rapy
alo
neIn
terv
enti
on P
DT
with
rad
ioth
erap
y: R
adio
ther
apy
for
4 w
k (4
0 G
y). T
hen
intr
aven
ous
haem
atop
orph
yrin
de
riva
tive
(5 m
g/kg
bw
) be
fore
ill
umin
atio
n w
ith 6
30-n
m r
ed li
ght
(400
–50
0 W/c
m2 a
t ea
ch p
art
of t
he t
umou
r fo
r 15
min
) at
48
and
72 h
rC
ompa
rato
r R
adio
ther
apy:
40 G
y fo
r 4
wk
Mor
talit
y T
he 5
-yr
surv
ival
rat
e w
as
29.9
% in
the
PD
T g
roup
com
pare
d w
ith
16.7
% (
p =
0.05
). The
10-
yr s
urvi
val r
ate
was
16.
7% in
the
PD
T g
roup
vs
10.0
%
(p <
0.0
5)M
orbi
dity
Not
ass
esse
dQ
oL a
nd r
etur
n to
nor
mal
act
ivit
y N
ot a
sses
sed
AE
s All
PDT
pat
ient
s ex
peri
ence
d pi
gmen
tatio
n, a
nd s
wel
ling
and
itchi
ness
. A
ll PD
T p
atie
nts
also
exp
erie
nced
pa
in w
hen
swal
low
ing
for
3–5
d (s
ome
patie
nts
had
pain
for
> 10
d
and
disc
ontin
ued
trea
tmen
t). 2
3 di
ed
in t
he P
DT
gro
up: l
oss
to F
U t
wo;
un
cont
rolle
d lo
calis
atio
n 13
incl
udin
g on
e du
e to
blo
ckag
e of
oes
opha
gus;
met
asta
ses
eigh
t; ot
her
dise
ase
one;
un
know
n ca
use
one.
26
died
in t
he
radi
othe
rapy
gro
up: l
oss
to F
U o
ne;
unco
ntro
lled
loca
lisat
ion
18, i
nclu
ding
tw
o du
e to
blo
ckag
e of
oes
opha
gus;
met
asta
ses
four
; oth
er d
isea
se t
wo;
un
know
n ca
use
two
Res
ourc
e us
e N
ot a
sses
sed
Aut
hors
’ con
clus
ions
Rad
ioth
erap
y co
mbi
ned
with
PD
T c
ould
obv
ious
ly
enha
nce
the
long
-ter
m s
urvi
val r
ate
of
patie
nts
with
adv
ance
d oe
soph
agea
l ca
ncer
Bri
ef s
tudy
app
rais
al T
his
was
a
brie
f rep
ort
and
som
e m
etho
dolo
gica
l as
pect
s w
ere
not
clea
rly
repo
rted
. T
he p
-val
ues
wer
e no
t re
port
ed
cons
iste
ntly
bet
wee
n th
e ab
stra
ct a
nd
the
text
mak
ing
it di
fficu
lt to
cla
rify
the
si
gnifi
cant
diff
eren
ces
betw
een
grou
ps
Appendix 17
264
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
265Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Zha
ng e
t al.
(200
7)11
3
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry C
hina
Lang
uage
Eng
lish
Stud
y de
sign
RC
TN
o. o
f par
tici
pant
sTo
tal:
140
Inte
rven
tion:
42
Com
para
tor:
98N
o. o
f rec
ruit
ing
cent
res
Not
sta
ted;
ap
pear
s to
be
two
cent
res
in C
hina
Follo
w-u
p pe
riod
an
d fr
eque
ncy
FU
at 1
mth
. Ove
r 70
%
patie
nts
wer
e fo
llow
ed
up fo
r 12
–36
mth
Trea
tmen
t in
tent
ion
Palli
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y A
dvan
ced
oeso
phag
ocar
diac
ca
rcin
oma
Mai
n el
igib
ility
cr
iter
ia B
iops
y pr
oven
adv
ance
d oe
soph
agea
l ca
rcin
oma
Pati
ent
char
acte
rist
ics
% M
ale:
79A
ge r
ange
: 40–
81 yr
Med
ian
age:
PDT
58;
PD
T w
ith 5
-FU
62
Can
cer
stag
e: St
age
II 84
; sta
ge II
I 53;
st
age
IV 3
Con
com
itan
t tr
eatm
ent
Not
st
ated
Tria
l tre
atm
ents
PD
T v
s PD
T w
ith 5
-FU
Inte
rven
tion
PD
T: A
fter
intr
aven
ous
inje
ctio
n of
the
pho
tose
nsiti
ser
PSD
-007
(p
hoto
carc
inor
in)
(3–5
mg/
kg b
w)
and
patie
nts
wer
e ke
pt in
the
dar
k. Ir
radi
atio
n w
as p
erfo
rmed
at
24 a
nd 4
8 hr
with
eith
er
630-
nm c
oppe
r va
pour
pum
ped-
dye
lase
r or
632
.8 n
m h
igh
pow
er H
e-N
e la
ser
(tot
al
dose
200
–400
J/cm
fibr
e le
ngth
, med
ian
300
J/cm
). Thi
s w
as d
eliv
ered
by
cylin
dric
al
diffu
sers
und
er e
ndos
cope
ass
ista
nce.
Ir
radi
atio
n w
as c
arri
ed o
ut in
one
to
four
se
gmen
ts (
with
slig
ht o
verl
ap b
etw
een
each
seg
men
t) d
epen
ding
on
lesi
on le
ngth
an
d di
ffuse
r. Tre
atm
ent
coul
d be
rep
eate
d af
ter
1 m
th u
nles
s ev
alua
tion
show
ed
effe
ctiv
enes
s or
sym
ptom
s w
ere
rem
itted
. Pa
tient
s w
ere
advi
sed
to a
void
sun
light
ex
posu
re fo
r ov
er 1
mth
Com
para
tor
PDT
with
5-F
U: A
s fo
r PD
T b
ut in
add
ition
, bef
ore
irra
diat
ion,
20
0–50
0 m
g 5-
FU w
as lo
cally
inje
cted
into
tu
mou
r tis
sue
unde
r en
dosc
opic
gui
danc
e.
Befo
re in
ject
ion
the
exte
nt o
f the
lesi
ons
was
con
firm
ed. M
ost
patie
nts
rece
ived
four
to
eig
ht in
ject
ions
per
tum
our
Mor
talit
y M
ean
surv
ival
tim
e w
as 8
.9 m
th
with
PD
T a
lone
com
pare
d w
ith 1
5.1
mth
fo
r PD
T a
nd 5
-FU
(p <
0.0
1)M
orbi
dity
The
rat
e of
dys
phag
ia
rem
issi
on w
as 8
7% fo
r PD
T c
ompa
red
with
99%
with
PD
T a
nd 5
-FU
(p
< 0.
05).
Diff
eren
ces
in p
hary
ngea
l pai
n an
d w
eigh
t lo
ss w
ere
not
sign
ifica
nt. W
ith P
DT
alo
ne
one
patie
nt a
chie
ved
com
plet
e re
mis
sion
(v
s fiv
e w
ith c
ombi
ned
ther
apy,
p <
0.05
), ei
ght
sign
ifica
nt r
emis
sion
(vs
36)
and
five
no
rem
issi
on (
vs n
ine)
. With
com
bine
d th
erap
y 48
pat
ient
s al
so a
chie
ved
min
or
rem
issi
onQ
oL a
nd r
etur
n to
nor
mal
act
ivit
y N
ot a
sses
sed
AE
s Su
bter
nal p
ain
due
to o
esop
hage
al
muc
osa
inju
ry a
nd g
astr
oeso
phag
eal r
eflux
1–
2 d
afte
r tr
eatm
ent
was
rep
orte
d by
se
ven
patie
nts
in P
DT
onl
y an
d ei
ght
patie
nts
in c
ombi
natio
n tr
eatm
ent
Eigh
t pa
tient
s in
tot
al a
ccid
enta
lly e
xpos
ed
them
selv
es t
o su
nlig
ht a
nd d
evel
oped
di
scol
orat
ion
of t
he s
kin
No
oeso
phag
eal s
teno
sis
or p
erfo
ratio
n re
port
ed in
eith
er g
roup
Res
ourc
e us
e N
ot a
sses
sed
Aut
hors
’ con
clus
ions
PD
T is
saf
e an
d ef
fect
ive
for
adva
nced
oes
opha
goca
rdia
c ca
ncer
. Its
the
rape
utic
effe
ct c
an b
e fu
rthe
r im
prov
ed w
hen
com
bine
d w
ith lo
cal
chem
othe
rapy
Bri
ef s
tudy
app
rais
al T
his
stud
y w
as p
oorl
y re
port
ed (
e.g.
met
hod
of
rand
omis
atio
n, w
heth
er IT
T a
naly
sis
was
us
ed)
but
mos
t im
port
antly
it a
ppea
rs t
hat
afte
r ov
er 4
0 pa
tient
s ha
d be
en t
reat
ed,
inte
rim
ana
lysi
s w
as c
arri
ed o
ut a
nd a
ll su
bseq
uent
pat
ient
s w
ere
trea
ted
with
co
mbi
ned
PDT
and
5-F
U. T
hese
ana
lyse
s w
ere
not
furt
her
repo
rted
. Giv
en t
his
shift
fr
om a
n R
CT
to
expe
rim
enta
l with
out
a co
mpa
rato
r it
is d
ifficu
lt to
det
erm
ine
the
relia
bilit
y of
the
stu
dy r
esul
ts o
vera
llTh
e au
thor
s’ co
nclu
sions
do
not f
ollo
w fr
om
the
resu
lts re
port
ed
Appendix 17
264
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
265
Appendix 18 Lung cancer data extraction
Appendix 18
266
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
267Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Baa
s et
al.
(199
4)12
1
Dat
a so
urce
Abs
trac
tC
ount
ry T
he
Net
herl
ands
Lang
uage
Eng
lish
Stud
y de
sign
RC
TN
o. o
f par
tici
pant
s To
tal:
39In
terv
entio
n: 1
5C
ompa
rato
r: 12
2nd
Com
para
tor:
12N
o. o
f Rec
ruit
ing
Cen
tres
Not
sta
ted
Follo
w-u
p pe
riod
and
fr
eque
ncy
Not
sta
ted
Trea
tmen
t in
tent
ion
Palli
ativ
eTy
pe o
f Lun
g C
ance
r an
d H
isto
logy
Non
-sm
all
cell;
no fu
rthe
r de
tails
gi
ven
Mai
n el
igib
ility
cri
teri
a H
isto
logi
cally
pro
ven
inop
erab
le lo
core
gion
al
NSC
LC, w
eigh
t lo
ss <
10%
an
d a
PS (
sic)
> 7
0%Pa
tien
t ch
arac
teri
stic
s%
Mal
e: 88
Con
com
itan
t tr
eatm
ent
Not
sta
ted
Tria
l tre
atm
ents
ERT
alo
ne v
s PD
T
prec
edin
g ER
T v
s H
DR
pre
cedi
ng E
RTIn
terv
enti
on P
hoto
frin
2 m
g/kg
, 20
0 J/c
m, 6
30 n
m g
iven
2 w
k be
fore
ERT
. O
ther
PD
T p
aram
eter
s no
t st
ated
Com
para
tor
ERT
alo
ne:
14 x
2.5
+ 8
x 2
.5 G
y to
the
tum
our
area
in
4 w
k2n
d co
mpa
rato
r H
DR
+ E
RT: A
s ab
ove
prec
eded
by
HD
R: 1
5 G
y at
1-c
m
dist
ance
alo
ng t
he t
umou
r 2
wk
befo
re
ERT
Mor
talit
y A
sses
sed
but
not
repo
rted
pe
r gr
oup
Mor
bidi
ty N
ot a
sses
sed
AE
s M
inor
hae
mop
tysi
s in
tw
o PD
T-ER
T p
atie
nts.
Skin
pho
tose
nsiti
vity
was
ac
cept
able
in p
atie
nts
trea
ted
with
PD
T
(no
data
pro
vide
d). O
ther
AEs
rep
orte
d bu
t no
t br
oken
dow
n by
gro
up
Aut
hors
’ con
clus
ions
No
conc
lusi
ons
spec
ific
to P
DT
Bri
ef s
tudy
app
rais
al T
his
smal
l st
udy
was
an
inte
rim
ana
lysi
s of
a R
CT
pr
esen
ted
in a
bstr
act
form
. Alth
ough
it
indi
cate
d th
at u
pdat
ed r
esul
ts w
ould
be
pre
sent
ed, n
o fu
rthe
r in
form
atio
n co
uld
be lo
cate
d. M
ost
of t
he s
tudy
’s m
etho
dolo
gica
l det
ails
wer
e no
t av
aila
ble
from
the
abs
trac
t an
d th
e m
ajor
ity o
f the
res
ults
wer
e no
t br
oken
do
wn
by t
reat
men
t gr
oup
Appendix 18
266
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
267Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Dia
z-Jim
enez
et a
l. (19
99)12
2
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry S
pain
Lang
uage
Eng
lish
Stud
y D
esig
nR
CT
No.
of p
arti
cipa
nts
Tota
l: 31
Inte
rven
tion:
14
Com
para
tor:
17N
o. o
f Rec
ruit
ing
Cen
tres
Not
sta
ted
Follo
w-u
p pe
riod
an
d fr
eque
ncy
FU a
t 1,
2, 3
, 6 a
nd
12 m
th (
and
18 m
th if
po
ssib
le)
Trea
tmen
t in
tent
ion
Palli
ativ
eTy
pes
of L
ung
Can
cer
and
His
tolo
gy N
on-s
mal
l cel
l 25
SCC
, thr
ee a
deno
carc
inom
a, th
ree
undi
ffere
ntia
ted
carc
inom
aM
ain
elig
ibili
ty c
rite
ria
Biop
sy-
prov
en in
oper
able
can
cer
with
tot
ally
or
par
tially
obs
truc
tive
endo
bron
chia
l le
sion
s w
ith o
r w
ithou
t ex
trab
ronc
hial
tu
mou
r. Pa
tient
s >
18 yr
, non
-pr
egna
nt, i
nfer
tile
or p
ostm
enop
ausa
l. K
arno
fsky
sta
tus ≥
40%
, ≥ 4
wk
from
la
st c
hem
othe
rapy
cyc
le a
nd ≥
3 w
k fr
om la
st r
adia
tion
dose
. Pat
ient
s w
ho
had
prev
ious
PD
T o
r N
d:YA
G w
ere
excl
uded
. Fur
ther
elig
ibili
ty c
rite
ria
wer
e re
port
edPa
tien
t ch
arac
teri
stic
s%
Mal
e: 10
0A
ge r
ange
: Not
sta
ted
Mea
n ag
e: 65
yrC
ance
r st
age:
Stag
e I,
four
pat
ient
s; st
age
II, o
ne; s
tage
IIIA
, six
; sta
ge II
IB,
10; s
tage
IV, s
even
No.
with
rec
urre
nt t
umou
r: th
ree
Con
com
itan
t tr
eatm
ent
Not
st
ated
Tria
l tre
atm
ents
PD
T v
s N
d:YA
G la
ser
rese
ctio
nIn
terv
enti
on
Intr
aven
ous
DH
E at
dos
e of
2 m
g/kg
with
630
-nm
ar
gon
dye
lase
r, 40
–50
hr
afte
r in
ject
ion.
Max
imum
of
thr
ee d
oses
(si
x ph
otor
adia
tions
). O
ther
pa
ram
eter
s no
t re
port
edC
ompa
rato
r N
d:YA
G
rese
ctio
n us
ing
15-
to
80-W
pul
ses
of 0
.5–1
.5 s.
Pr
oced
ure
repe
ated
ev
ery
2–4
d as
nec
essa
ry
Mor
talit
y Su
rviv
al s
igni
fican
tly
long
er in
PD
T g
roup
(26
5 vs
95
d, p
= 0
.007
). 4/
14 (
PDT
) an
d 4/
17
(Nd:
YAG
) st
ill a
live
at e
nd o
f stu
dyM
orbi
dity
Sim
ilar
resp
onse
in
both
gro
ups:
38.5
% P
DT
vs
23.5
%
Nd:
YAG
at
1 m
th (
p =
ns).
PR
at 1
mth
in t
hree
PD
T a
nd fo
ur
Nd:
YAG
pat
ient
s. C
R a
t 1
mth
in
one
PDT
pat
ient
. Tim
e el
apse
d un
til
trea
tmen
t fa
ilure
: 50
d (P
DT
) vs
38
d (N
d:YA
G)
(p =
0.0
3)Q
oL a
nd r
etur
n to
nor
mal
ac
tivi
ty A
sses
sed
but
not
repo
rted
AE
s Br
onch
itis
was
the
mos
t co
mm
on (
four
cas
es in
PD
T g
roup
, on
e in
Nd:
YAG
gro
up)
Phot
osen
sitis
atio
n in
four
PD
T
patie
nts.
Five
pat
ient
s ha
d no
AEs
, al
l in
Nd:
YAG
gro
up. O
ne d
eath
pr
obab
ly r
elat
ed t
o PD
T
Aut
hors
’ con
clus
ions
PD
T is
a v
alid
met
hod
of
palli
atio
n in
par
tially
or
tota
lly o
bstr
uctin
g N
SCLC
Bri
ef s
tudy
app
rais
al D
ifficu
lt to
eva
luat
e re
sults
due
to
impo
rtan
t ba
selin
e di
ffere
nces
(p
rese
nce
of c
ough
, and
sta
ge o
f can
cer)
bet
wee
n gr
oups
. Kar
nofs
ky p
erfo
rman
ce a
nd F
U a
fter
1 m
th
asse
ssed
but
not
rep
orte
d. N
o de
tails
on
blin
ding
Appendix 18
268
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
269Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Lam
et a
l., (1
991)
123
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry C
anad
aLa
ngua
ge E
nglis
hSt
udy
desi
gn R
CT
No.
of p
arti
cipa
nts
Tota
l: 41
Inte
rven
tion:
20
Com
para
tor:
21N
o. o
f Rec
ruit
ing
Cen
tres
Not
sta
ted
Follo
w-u
p pe
riod
an
d fr
eque
ncy
FU
at 1
, 2, 3
, 6, 1
2, 1
8 an
d 24
mth
Trea
tmen
t in
tent
ion
Palli
ativ
eTy
pes
of L
ung
Can
cer
and
His
tolo
gy N
on-s
mal
l ce
ll 34
squ
amou
s ce
ll, th
ree
aden
ocar
cino
ma,
four
larg
e ce
llM
ain
elig
ibili
ty c
rite
ria
Biop
sy-p
rove
n st
age
III n
on-s
mal
l ce
ll br
onch
ogen
ic c
arci
nom
a w
ith o
bstr
uctin
g or
par
tially
ob
stru
ctin
g en
dobr
onch
ial l
esio
n.
Kar
nofs
ky r
atin
g ≥
40 a
nd a
bilit
y to
to
lera
te m
ultip
le b
ronc
hosc
opie
s. Pa
tient
s w
ho h
ad p
revi
ous
PDT
or
rad
ioth
erap
y, or
con
curr
ent
chem
othe
rapy
or
Nd:
YAG
lase
r th
erap
y w
ere
excl
uded
, as
wer
e pa
tient
s w
hose
tum
ours
wer
e in
vasi
ve t
o m
ajor
blo
od v
esse
ls o
n C
T s
can
Pati
ent
char
acte
rist
ics
% M
ale:
76M
ean
age:
Aro
und
67 yr
Tum
our
loca
tion:
78%
in m
ain
stem
br
onch
us, 2
2% in
loba
r br
onch
usC
onco
mit
ant
trea
tmen
t Se
e ‘E
ligib
ility
cri
teri
a’
Tria
l tre
atm
ents
PD
T +
radi
othe
rapy
vs
Rad
ioth
erap
y al
one
Inte
rven
tion
Intr
aven
ous
Phot
ofri
n at
2 m
g/kg
follo
wed
w
ith 4
0–50
hr
of r
ed (
630n
m)
light
from
arg
on-d
ye la
ser
deliv
ered
by
a si
ngle
-ste
p in
dex
quar
tz fi
bre
inse
rted
into
the
bi
opsy
cha
nnel
of a
flex
ible
fib
reop
tic b
ronc
hosc
ope
(a
cylin
dric
al d
iffus
er t
ip w
as
inse
rted
1–2
cm in
to t
umou
r).
Pow
er d
ensi
ty w
as 4
00 m
W/c
m,
tota
l lig
ht d
ose
was
200
J/cm
. R
esid
ual t
umou
r tr
eate
d by
a
repe
at li
ght
expo
sure
The
dur
atio
n of
ligh
t w
as n
ot
stat
ed. R
adio
ther
apy
– se
e be
low
Com
para
tor
Rad
iatio
n at
30
00 cG
y in
10
frac
tions
with
a
4-M
eV li
near
acc
eler
ator
ov
er 2
wk,
usin
g a
para
llel p
air
tech
niqu
e. F
ield
siz
e de
fined
by
the
50%
isod
ose
line
with
2-c
m
mar
gin
of n
orm
al t
issu
e
Mor
talit
y 16
pat
ient
s di
ed in
rad
ioth
erap
y-al
one
grou
p co
mpa
red
with
14
in P
DT
+ ra
diot
hera
py
grou
p, in
bot
h gr
oups
eig
ht d
eath
s w
ere
due
to
met
asta
ses.
Thr
ee p
atie
nts
in t
he P
DT
+ ra
diot
hera
py
grou
p di
ed fr
om m
assi
ve h
aem
opty
sis
(67,
187
and
56
7 d,
res
pect
ivel
y, af
ter
trea
tmen
t), c
ompa
red
with
no
ne in
the
Rad
ioth
erap
y-al
one
grou
p. N
o di
ffere
nce
betw
een
grou
ps in
med
ian
surv
ival
tim
es (
444
d in
PD
T +
radi
othe
rapy
vs
445
d in
Rad
ioth
erap
y-al
one
grou
p)M
orbi
dity
Sig
nific
antly
gre
ater
red
uctio
n of
ha
emop
tysi
s an
d sh
ortn
ess
of b
reat
h, a
nd c
ough
at
1 an
d 3
mth
, in
the
PDT
+ ra
diot
hera
py g
roup
(p
< 0.
05)
14/2
0 PD
T +
radi
othe
rapy
and
2/2
1 ra
diot
hera
py
alon
e ac
hiev
ed c
ompl
ete
re-o
peni
ng o
f bro
nchi
al
lum
en. F
our
patie
nts
in R
adio
ther
apy-
alon
e gr
oup
faile
d to
res
pond
to
trea
tmen
t, no
ne fa
iled
in
PDT
+ ra
diot
hera
py g
roup
Med
ian
inte
rval
bet
wee
n tr
eatm
ent
and
loca
l rec
urre
nce
was
sig
nific
antly
long
er in
PD
T +
radi
othe
rapy
gro
up (
233
d vs
107
d, p
= 0
.005
)Q
oL a
nd r
etur
n to
nor
mal
act
ivit
y A
sses
sed
but
not
repo
rted
(K
arno
fsky
per
form
ance
)A
Es
Phot
osen
sitiv
ity w
ith m
ild e
ryth
ema,
whi
ch
reso
lved
with
out
trea
tmen
t, w
as s
een
in fo
ur o
f the
PD
T +
radi
othe
rapy
gro
up
Aut
hors
’ con
clus
ions
T
he a
dditi
on o
f PD
T p
rior
to
rad
ioth
erap
y pr
ovid
es
sign
ifica
ntly
bet
ter
and
long
er-la
stin
g lo
cal c
ontr
ol
than
rad
ioth
erap
y al
one
Bri
ef s
tudy
app
rais
al
No
deta
ils o
f met
hods
of
rand
omis
atio
n, a
lloca
tion
conc
ealm
ent
or b
lindi
ng
wer
e re
port
ed fo
r th
is s
mal
l st
udy
(rai
sing
rel
iabi
lity
issu
es).
Som
e ou
tcom
es
asse
ssed
but
not
rep
orte
d
Appendix 18
268
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
269
Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Lam
et a
l. (1
987)
124
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry C
anad
aLa
ngua
ge E
nglis
hSt
udy
desi
gn R
CT
No.
of p
arti
cipa
nts
Tota
l: 11
Inte
rven
tion:
Fiv
eC
ompa
rato
r: Si
xN
o. o
f Rec
ruit
ing
Cen
tres
Not
sta
ted
Follo
w-u
p pe
riod
and
fr
eque
ncy
FU a
t 4
and
12 w
k, th
en q
uart
erly
th
erea
fter
(unl
ess
prog
ress
ion
of t
umou
r oc
curs
)
Trea
tmen
t in
tent
ion
Palli
ativ
eTy
pes
of L
ung
Can
cer
and
His
tolo
gy N
on-s
mal
l ce
ll: ni
ne s
quam
ous
cell,
two
larg
e ce
llM
ain
elig
ibili
ty c
rite
ria
Patie
nts
with
inop
erab
le
non-
smal
l cel
l bro
ncho
geni
c ca
rcin
oma,
part
ially
or
com
plet
ely
obst
ruct
ing
a ce
ntra
l air
way
, who
had
re
ceiv
ed n
o pr
ior
trea
tmen
t (e
.g. c
hem
othe
rapy
or
radi
othe
rapy
). Pa
tient
s w
ith e
vide
nce
of m
etas
tatic
di
seas
e w
ere
excl
uded
Pati
ent
char
acte
rist
ics
% M
ale:
82M
ean
age:
66 yr
All
patie
nts
had
tum
ours
at
mor
e th
an o
ne s
iteC
onco
mit
ant
trea
tmen
t N
ot s
tate
d
Tria
l tre
atm
ents
PD
T +
radi
othe
rapy
vs
Rad
ioth
erap
y al
one
Inte
rven
tion
Intr
aven
ous
Phot
ofri
n II
24–4
8 hr
pri
or t
o re
d lig
ht (
630
nm)
from
a c
ontin
uous
arg
on p
umpe
d-dy
e la
ser,
via
sing
le-s
tep
inde
x qu
artz
fibr
es
inse
rted
into
cha
nnel
of a
dou
ble
lum
en fl
exib
le fi
breo
ptic
bro
ncho
scop
e (o
r a
sing
le c
hann
el in
stru
men
t). A
cy
lindr
ical
diff
user
tip
(0.
5, 1
.0 o
r 1.
5 cm
) w
as in
sert
ed in
to t
he t
umou
r. Po
wer
den
sity
was
400
mW
/cm
and
to
tal l
ight
dos
e 30
0 J/c
m. C
lean
-up
bron
chos
copy
follo
wed
2 d
late
r, w
ith
furt
her
light
at
300
J/cm
(bu
t no
mor
e Ph
otof
rin
II) fo
r an
y re
sidu
al t
umou
rs.
PDT
was
giv
en 1
st, w
ith r
adio
ther
apy
star
ting
with
in 1
wk
of P
DT
Tum
ours
tha
t co
uld
not
be in
sert
ed
due
to s
mal
l siz
e, o
r ha
rdne
ss,
rece
ived
200
J/cm
2 at
pow
er d
ensi
ty o
f 20
0 m
W/c
m2 u
sing
mic
role
ns fi
bre
The
dos
e of
Pho
tofr
in a
nd d
urat
ion
of
light
wer
e no
t st
ated
. For
rad
ioth
erap
y, se
e be
low
Com
para
tor A
ll pa
tient
s ha
d 30
00 cG
y in
10
frac
tions
ove
r 2
wk
usin
g a
para
llel-p
air
tech
niqu
e fr
om
a 4
MeV
line
ar a
ccel
erat
or. F
ield
siz
e de
fined
by
the
50%
isod
ose
line
with
2-
cm m
argi
n of
nor
mal
tis
sue
Mor
talit
y O
ne p
atie
nt d
ied
in t
he
PDT
+ ra
diot
hera
py g
roup
vs
thre
e in
th
e R
adio
ther
apy-
alon
e gr
oup
Mor
bidi
ty B
oth
grou
ps h
ad
sign
ifica
ntly
impr
oved
res
pira
tory
sy
mpt
oms
at 4
wk
(with
mea
n sc
ores
falli
ng fr
om 7
to
1 in
the
PD
T +
radi
othe
rapy
gro
up, a
nd 7
to
4 in
the
Rad
ioth
erap
y-al
one
grou
p, p
< 0.
05). T
he m
ean
scor
e fo
r th
e R
adio
ther
apy-
alon
e gr
oup
was
bac
k up
to
7 at
12
wk,
but
the
PDT
+ ra
diot
hera
py g
roup
had
a m
ean
scor
e of
2, w
hich
was
sig
nific
antly
di
ffere
nt fr
om b
asel
ine
(p <
0.0
5)A
t 4
wk,
the
PDT
+ ra
diot
hera
py
grou
p ha
d a
sign
ifica
nt r
educ
tion
in%
ai
rway
obs
truc
tion
(99
vs 2
1) a
nd
impr
ovem
ent
in a
rter
ial o
xyge
n (6
3 vs
80,
bot
h p
< 0.
05)
whe
n co
mpa
red
to b
asel
ine,
with
per
cent
age
airw
ay
obst
ruct
ion
still
sig
nific
antly
impr
oved
at
12
wk
(99
vs 2
5, p
< 0
.05)
. The
re
wer
e no
sig
nific
ant
redu
ctio
ns in
the
R
adio
ther
apy-
alon
e gr
oup
QoL
and
ret
urn
to
norm
al a
ctiv
ity
At
4 w
k, th
e PD
T +
radi
othe
rapy
pat
ient
s ha
d si
gnifi
cant
impr
ovem
ents
(p
< 0.
05)
in
both
Kar
nofs
ky r
atin
g (7
8 vs
93)
and
Q
oL (
56 v
s 39
), co
mpa
red
to b
asel
ine
scor
es. T
here
wer
e no
sig
nific
ant
diffe
renc
es in
the
Rad
ioth
erap
y-al
one
grou
pA
Es
One
pat
ient
rec
eivi
ng P
DT
re
mai
ned
phot
osen
sitiv
e fo
r 8
wk
Aut
hors
’ con
clus
ions
The
add
ition
of
PD
T p
rior
to
radi
othe
rapy
pro
vide
s si
gnifi
cant
ly b
ette
r an
d lo
nger
-la
stin
g pa
lliat
ion,
tha
n ra
diot
hera
py
alon
e, fo
r pa
tient
s w
ith o
bstr
uctiv
e en
dobr
onch
ial t
umou
rs. T
he c
ombi
ned
trea
tmen
t m
ay a
lso
impr
ove
surv
ival
Bri
ef s
tudy
app
rais
al V
ery
smal
l sa
mpl
e si
ze c
oupl
ed w
ith p
oorl
y re
port
ed m
etho
ds m
ake
it di
fficu
lt to
dr
aw a
ny r
obus
t co
nclu
sion
s
Appendix 18
270 Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Ler
oy e
t al.
(199
8)12
5
Link
ed p
ublic
atio
ns21
2
Dat
a so
urce
Abs
trac
tC
ount
ry N
ot s
tate
dLa
ngua
ge E
nglis
hSt
udy
desi
gn R
CT
No.
of p
arti
cipa
nts
Tota
l: 14
1In
terv
entio
n: N
ot s
tate
dC
ompa
rato
r: N
ot s
tate
dN
o. o
f Rec
ruit
ing
Cen
tres
Not
sta
ted
Follo
w-u
p pe
riod
and
fr
eque
ncy
FU a
t 1
wk
and
1 m
th
Trea
tmen
t in
tent
ion
Palli
ativ
eTy
pe o
f Lun
g C
ance
r an
d H
isto
logy
Non
-sm
all
cell
Mai
n el
igib
ility
cr
iter
ia N
ot s
tate
dPa
tien
t ch
arac
teri
stic
s N
ot
stat
edC
onco
mit
ant
trea
tmen
t N
ot
stat
ed
Tria
l tre
atm
ents
PD
T v
s N
d:YA
G
lase
rIn
terv
enti
on 2
mg/
kg o
f Pho
tofr
in
follo
wed
48
hr la
ter
by li
ght
activ
atio
nLi
ght
sour
ce a
nd d
urat
ion,
wav
elen
gth
of li
ght,
pow
er d
ensi
ty, t
otal
ligh
t do
se,
max
imum
no.
of s
essi
ons
allo
wed
, and
po
stop
erat
ive
advi
ce n
ot s
tate
dC
ompa
rato
r N
o de
tails
pro
vide
d
Mor
talit
y N
ot a
sses
sed
Mor
bidi
ty C
R +
PR
com
para
ble
betw
een
grou
ps a
t w
k 1
(PD
T 6
5% v
s N
d:YA
G 6
1%),
but
sign
ifica
ntly
diff
eren
t at
1 m
th (
PDT
61%
vs
Nd:
YAG
35%
, p
< 0.
05).
At
1 m
th P
DT
als
o im
prov
ed
sym
ptom
s of
dys
pnoe
a (2
8% v
s 13
%),
coug
h (3
3% v
s 11
%),
haem
opty
sis
(33%
vs
19%
), an
d sp
utum
pro
duct
ion
(22%
vs
14%
), p-
valu
es n
ot s
tate
dQ
oL a
nd r
etur
n to
nor
mal
act
ivit
y N
ot a
sses
sed
AE
s M
ild-t
o-m
oder
ate
skin
ph
otos
ensi
tivity
in 2
1% o
f PD
T p
atie
nts.
No
furt
her
deta
ils
Aut
hors
’ con
clus
ions
Pho
tofr
in is
at
leas
t si
mila
r to
or
bett
er t
han
Nd:
YAG
th
erm
al a
blat
ion
in r
e-es
tabl
ishi
ng t
he
pate
ncy
of t
he o
bstr
ucte
d lu
men
and
pa
lliat
ing
sym
ptom
s at
wk
1 an
d m
th 1
fo
llow
ing
trea
tmen
tB
rief
stu
dy a
ppra
isal
The
ver
y lim
ited
info
rmat
ion
prov
ided
, pa
rtic
ular
ly o
n st
udy
met
hods
and
ba
sic
resu
lts (
e.g.
no n
umbe
rs o
n ra
ndom
isat
ion
by t
reat
men
t gr
oup)
m
akes
ass
essm
ent
of r
elia
bilit
y di
fficu
lt
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
271
Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Mai
er e
t al.
(200
2)12
7
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry A
ustr
iaLa
ngua
ge E
nglis
hSt
udy
desi
gn N
on-
RC
TN
o. o
f par
tici
pant
sTo
tal:
40In
terv
entio
n: 1
6C
ompa
rato
r: 24
No.
of R
ecru
itin
g C
entr
es O
neFo
llow
-up
peri
od
and
freq
uenc
y 1
wk
and
4 w
k
Trea
tmen
t in
tent
ion
Palli
ativ
eTy
pe o
f Lun
g C
ance
r an
d H
isto
logy
Non
-sm
all c
ell
Mai
n el
igib
ility
cri
teri
a Pa
tient
s w
ith m
alig
nant
tra
cheo
bron
chia
l st
enos
is, n
ot e
ligib
le fo
r re
sect
ion
trea
tmen
t be
caus
e of
poo
r pe
rfor
man
ce s
tatu
s, fu
nctio
nal a
nd/
or a
nato
mic
al in
oper
abili
ty, a
nd/o
r re
fusi
ng s
urge
ryPa
tien
t ch
arac
teri
stic
s%
Mal
e: 75
Mea
n ag
e: A
LA, 6
4 yr
; Pho
tosa
n,
66 yr
Can
cer
stag
e: St
age
IIb, s
even
; Sta
ge
IIIa,
13; S
tage
IIIb
, six
; Sta
ge IV
, 14
Squa
mou
s ce
ll 27
, Ade
noca
rcin
oma
10, L
arge
cel
l car
cino
ma
thre
eSt
enos
is m
ean
(ran
ge):
ALA
, 79%
(5
0–90
%);
Phot
osan
, 50%
(20
–95%
)22
pat
ient
s w
ith r
adio
logi
cal
and
clin
ical
sig
ns o
f pos
tste
notic
pn
eum
onia
Kar
nofs
ky s
tatu
s m
ean
(ran
ge):
ALA
, 78
(60–
90);
Phot
osan
, 70
(60–
80)
Furt
her
patie
nt c
hara
cter
istic
s w
ere
repo
rted
Con
com
itan
t tr
eatm
ent
At
leas
t 4
wk
afte
r co
mbi
ned
PDT
/H
BO, a
ll pa
tient
s w
ere
cons
ider
ed
for
furt
her
trea
tmen
t, in
clud
ing
high
-dos
e ra
te b
rach
yrad
ioth
erap
y, ex
tern
al b
eam
irra
diat
ion
and/
or
chem
othe
rapy
Tria
l tre
atm
ents
PD
T w
ith 5
-ALA
an
d H
BO v
s PD
T w
ith P
hoto
san
and
HBO
Inte
rven
tion
ALA
was
ora
lly
adm
inis
tere
d at
a d
ose
of 6
0 m
g/kg
, 6–
8 hr
pri
or t
o PD
TIn
cas
es o
f sev
ere
tum
our
sten
osis
, PD
T w
as c
arri
ed o
ut b
y us
ing
a fib
re
with
a 2
-cm
tip
rad
ial l
ight
-diff
usin
g cy
linde
r, w
hich
was
inse
rted
thr
ough
th
e bi
opsy
cha
nnel
of t
he e
ndos
cope
. In
cas
es o
f mod
erat
e tu
mou
r st
enos
is
a 2-
cm b
allo
on a
pplic
ator
sys
tem
w
as u
sed
for
hom
ogen
eous
ligh
t di
stri
butio
n. D
urin
g tr
eatm
ent
the
radi
al li
ght
diffu
sing
cyl
inde
r an
d/or
ba
lloon
app
licat
or s
yste
m w
as c
lose
ly
appl
ied
to t
he s
urfa
ce o
f the
tum
our.
The
ligh
t do
se w
as 1
00 J/
cm2 .
Ligh
t at
630
nm
was
app
lied
by a
KT
P-N
d:
YAG
lase
r w
ith a
DY
E m
odul
e. In
bo
th g
roup
s ad
ditio
nal h
yper
bari
c ox
ygen
atio
n at
a le
vel o
f 2 A
TA in
a
wal
k-in
hyp
erba
ric
cham
ber
was
un
dert
aken
. Oxy
gen
was
app
lied
usin
g a
Scub
a va
lve
syst
em. E
ach
trea
tmen
t w
as p
erfo
rmed
und
er
shor
t-te
rm in
trav
enou
s an
aest
hesi
a w
ith e
ndot
rach
eal i
ntub
atio
n an
d sp
onta
neou
s br
eath
ing.
Skin
pr
otec
tion
was
man
aged
by
use
of a
ca
mou
flage
(C
over
mar
k, M
ilan,
Ital
y)
for
24 h
r af
ter
phot
osen
sitis
atio
nC
ompa
rato
r Ph
otos
an-3
was
ad
min
iste
red
intr
aven
ously
at
a do
sage
of 2
mg/
kg, 4
8 hr
pri
or t
o PD
T. Se
e in
terv
entio
n fo
r de
tails
of P
DT
de
liver
y. Sk
in p
rote
ctio
n w
as b
y us
ing
a co
mm
erci
ally
ava
ilabl
e su
n bl
ocke
r fo
r 12
wk
Mor
talit
y T
he m
ean
surv
ival
for
the
ALA
gro
up w
as 9
mth
and
the
Ph
otos
an g
roup
14
mth
(p
= 0.
020)
Mor
bidi
ty 4
wk
FUIn
the
ALA
gro
up, s
teno
sis
diam
eter
dr
oppe
d fr
om a
mea
n va
lue
of 7
9%
to 6
3%. I
n th
e Ph
otos
an g
roup
the
m
ean
valu
e dr
oppe
d fr
om 5
0% t
o 19
%,
p =
0.00
073,
in fa
vour
of P
hoto
san.
D
yspn
oea
was
impr
oved
in 1
0/16
ALA
pa
tient
s an
d 19
/24
Phot
osan
pat
ient
s. H
aem
opty
sis
subs
ided
in 1
3/16
ALA
pa
tient
s an
d 20
/24
Phot
osan
pat
ient
s. R
adio
logi
cal a
nd c
linic
al s
igns
of
post
sten
otic
pne
umon
ia s
ubsi
ded
in
5/9
ALA
pat
ient
s an
d 9/
13 P
hoto
san
patie
nts.
The
re w
as n
o st
atis
tical
ly
sign
ifica
nt d
iffer
ence
bet
wee
n gr
oups
on
pul
mon
ary
func
tion
para
met
ers
QoL
and
ret
urn
to n
orm
al
acti
vity
Mea
n K
arno
fsky
val
ue
chan
ged
from
78
to 7
9 in
the
ALA
gr
oup,
and
from
70
to 7
8 in
the
Ph
otos
an g
roup
, sho
win
g a
sign
ifica
nt
diffe
renc
e in
favo
ur o
f the
Pho
tosa
n gr
oup
(p =
0.0
0015
). O
ne p
atie
nt h
ad
an im
prov
emen
t of
10%
in t
he A
LA
grou
p, w
here
as 1
1 pa
tient
s in
the
Ph
otos
an g
roup
impr
oved
by
10%
an
d fiv
e im
prov
ed b
y 20
%. N
one
of
the
patie
nts
in t
he P
hoto
san
grou
p re
port
ed a
dec
reas
e in
QoL
due
to
long
-last
ing
need
for
skin
pro
tect
ion
AE
s N
o su
nbur
n oc
curr
ed in
eith
er
grou
p. N
o m
ajor
com
plic
atio
ns
rela
ting
to p
hoto
sens
itisa
tion,
PD
T
or H
BO w
ere
obse
rved
. Min
or
com
plic
atio
ns w
ere:
feve
r in
the
af
tern
oon
afte
r PD
T (
12 in
ALA
gro
up,
18 in
Pho
tosa
n gr
oup)
and
mild
che
st
pain
for
1 or
2 d
(6
in t
he A
LA g
roup
an
d 13
in t
he P
hoto
san
grou
p). N
one
of t
he A
Es r
equi
red
spec
ific
trea
tmen
t
Aut
hors
’ con
clus
ions
Pho
tosa
n se
ems
to b
e m
ore
effe
ctiv
e th
an A
LA
in P
DT
of m
alig
nant
tra
cheo
bron
chia
l st
enos
is. H
owev
er, t
hese
res
ults
wou
ld
need
con
firm
ing
in a
ran
dom
ised
, bl
inde
d tr
ial
Bri
ef s
tudy
app
rais
al T
his
smal
l pi
lot
stud
y w
as n
on-r
ando
mis
ed a
nd
the
grou
ps h
ad d
iffer
ence
s at
bas
elin
e w
hich
may
hav
e im
pact
ed o
n re
sults
. T
he s
urvi
val d
ata
do n
ot s
olel
y re
flect
the
effe
ctiv
enes
s of
the
PD
T
trea
tmen
t, as
4 w
k af
ter
PDT
pat
ient
s w
ere
elig
ible
to
rece
ive
a va
riet
y of
oth
er t
reat
men
ts. T
here
are
als
o do
ubts
as
to w
heth
er t
he A
LA d
osag
e w
as o
ptim
al
ATA
, atm
osph
ere
abso
lute
.
Appendix 18
272
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
273
Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Mog
hiss
i et
al. (
1993
)126
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry U
K
Lang
uage
Eng
lish
Stud
y de
sign
RC
TN
o. o
f par
tici
pant
sTo
tal:
26In
terv
entio
n: 1
5C
ompa
rato
r: 11
No.
of R
ecru
itin
g C
entr
es N
ot s
tate
dFo
llow
-up
peri
od
and
freq
uenc
y A
t 1,
2
and
3 m
th, t
hen
at
3-m
onth
ly in
terv
als
Trea
tmen
t in
tent
ion
Palli
ativ
eTy
pe o
f Lun
g C
ance
r an
d H
isto
logy
Non
-sm
all c
ell
Mai
n el
igib
ility
cri
teri
a St
age
III in
oper
able
NSC
LC w
ith >
50%
in
tral
umin
al b
ronc
hial
obs
truc
tion
Pati
ent
char
acte
rist
ics
% M
ale:
81A
ge r
ange
: 43–
76 yr
Mea
n ag
e: In
terv
entio
n 60
, co
mpa
rato
r 66
(ns
)C
onco
mit
ant
trea
tmen
t So
me
patie
nts
had
addi
tiona
l mod
aliti
es o
f tr
eatm
ent
afte
r 1
mth
Tria
l tre
atm
ents
PD
T v
s N
d:YA
G
lase
rIn
terv
enti
on In
trav
enou
s Ph
otof
rin
or P
hoto
frin
II a
t do
se o
f 2 m
g/kg
fo
llow
ed 4
8–54
hr
late
r by
red
ligh
t (6
30 n
m)
from
a c
oppe
r va
pour
pu
mpe
d-dy
e la
ser
deliv
ered
thr
ough
a
600-
nm q
uart
z fib
re w
ith a
te
rmin
al c
ylin
dric
al d
iffus
er. D
ose
of
200
J/cm
at
400
mW
/cm
. Dur
atio
n of
lig
ht d
ose
was
500
s. F
urth
er s
essi
ons
prov
ided
if n
eede
d. T
horo
ugh
debr
idem
ent
and
phys
ioth
erap
y af
ter
trea
tmen
t. C
aref
ul c
ouns
ellin
g on
ph
otos
ensi
tivity
Com
para
tor
Nd:
YAG
lase
r (F
ibre
lase
100
, Pilk
ingt
on)
with
a
400-µ
m d
iam
eter
del
iver
y fib
re
usin
g 40
–50 W
pul
ses
of 3
–5 s.
Dos
e de
pend
ent
on e
xten
t of
tum
our.
Furt
her
sess
ions
pro
vide
d if
need
ed
Mor
talit
y N
o tr
eatm
ent-
rela
ted
mor
talit
y. Lo
nger
-ter
m m
orta
lity
not
asse
ssed
Mor
bidi
ty A
t 1-
mth
, lum
inal
di
amet
er, a
s pe
rcen
tage
of n
orm
al
diam
eter
, was
sig
nific
antly
gre
ater
in
PDT
gro
up (
83%
) th
an t
he N
d:YA
G
grou
p (6
1%),
p <
0.00
06. B
oth
FVC
an
d FE
V1 i
mpr
oved
sig
nific
antly
mor
e w
ith P
DT
1 m
th a
fter
trea
tmen
t w
hen
com
pare
d to
pre
-tre
atm
ent
mea
sure
men
ts: m
ean
diffe
renc
e in
FV
C, 0
.47
PDT
vs
–0.0
6 N
d:YA
G,
p <
0.05
, mea
n di
ffere
nce
in F
EV1,
0.35
PD
T v
s 0.
01 N
d:YA
G, p
< 0
.05
All
patie
nts
had
a PR
at
1 m
thA
Es
No
seri
ous
post
-tre
atm
ent
com
plic
atio
ns. M
ild fe
ver
in
two
Nd:
YAG
pat
ient
s. N
o ph
otos
ensi
tivity
in P
DT
pat
ient
s
Aut
hors
’ con
clus
ions
PD
T is
m
ore
effe
ctiv
e th
an N
d:YA
G in
pa
tient
s w
ith e
xten
sive
obs
truc
tive
lung
can
cer
Bri
ef s
tudy
app
rais
al A
sm
all
stud
y w
ith n
o de
tails
of m
etho
ds
of r
ando
mis
atio
n, a
lloca
tion
conc
ealm
ent
or b
lindi
ng (
rais
ing
relia
bilit
y is
sues
)
Appendix 18
272
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
273
Appendix 19 Biliary tract cancer data extraction
Appendix 19
274
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
275Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Dec
hene
et a
l. (2
007)
132
Dat
a so
urce
Abs
trac
tC
ount
ry N
ot s
tate
dLa
ngua
ge E
nglis
hSt
udy
desi
gn N
on-R
CT
No.
of p
arti
cipa
nts
Tota
l: 29
Inte
rven
tion:
16
Com
para
tor:
13N
o. o
f rec
ruit
ing
cent
res
Not
sta
ted
Follo
w-u
p pe
riod
and
fr
eque
ncy
Not
sta
ted
Trea
tmen
t in
tent
ion
Palli
ativ
eTy
pe(s
) of
Can
cer
and
His
tolo
gyN
on-r
esec
tabl
e bi
le d
uct
canc
erM
ain
Elig
ibili
ty C
rite
ria
Adv
ance
d bi
le d
uct
canc
er
(no
furt
her
deta
ils g
iven
)Pa
tien
t ch
arac
teri
stic
s%
Mal
e: 76
Med
ian
age:
67–7
0H
isto
logi
cal c
onfir
mat
ion
was
not
re
port
edC
onco
mit
ant
trea
tmen
t Pe
ri-in
terv
entio
nal a
ntib
iotic
pr
ophy
laxi
s
Tria
l tre
atm
ents
PD
T w
ith
Phot
osan
-3 v
s PD
T w
ith P
hoto
frin
IIIn
terv
enti
on 2
mg/
kg P
hoto
san-
3 ad
min
iste
red
48 h
r be
fore
rad
iatio
n.
A 4
-cm
qua
rtz
fibre
and
a d
iode
la
ser
syst
em (
635
nm; 1
, 1 W
, 22
0 J/c
m).
Ligh
t pr
otec
tion
was
ad
vise
d fo
r 4–
6 w
k. Fu
rthe
r PD
T
para
met
ers
wer
e no
t re
port
edC
ompa
rato
r 2
mg/
kg P
hoto
frin
II
adm
inis
tere
d 48
hr
befo
re
radi
atio
n. A
4-c
m q
uart
z fib
re a
nd
a di
ode
lase
r sy
stem
(63
5 nm
; 1,
1 W, 2
20 J/
cm).
Ligh
t pr
otec
tion
was
ad
vise
d fo
r 4–
6 w
k. Fu
rthe
r PD
T
para
met
ers
wer
e no
t re
port
ed
Mor
talit
y M
edia
n su
rviv
al in
the
PS
-3 g
roup
was
690
d (
95%
CI 4
48
to 9
31)
and
in t
he P
F2 g
roup
it w
as
494
d (9
5% C
I 84
to 9
03),
p =
NS
Mor
bidi
ty N
ot a
sses
sed
QoL
and
ret
urn
to n
orm
al
acti
vity
Not
ass
esse
dA
Es T
here
was
no
subs
tant
ial
skin
rea
ctio
n ob
serv
ed (
no d
ata
prov
ided
). 23
% o
f pat
ient
s in
the
PF2
gr
oup
and
26%
of p
atie
nts
in t
he
PS3
grou
p de
velo
ped
‘con
side
rabl
e’
chol
angi
tisR
esou
rce
use
Not
ass
esse
d
Aut
hors
’ con
clus
ions
PD
T h
as t
he
pote
ntia
l to
cons
ider
ably
pro
long
su
rviv
al in
non
-res
ecta
ble
bile
duc
t ca
ncer
. The
effe
ct is
not
dep
ende
nt
on t
he t
ype
of h
aem
atop
orph
yrin
ph
otos
ensi
tiser
Bri
ef s
tudy
app
rais
al T
his
stud
y w
as r
epor
ted
in a
bstr
act
form
on
ly a
nd d
id n
ot p
rovi
de d
etai
ls o
f m
etho
dolo
gy s
uch
as r
ando
mis
atio
n,
blin
ding
and
allo
catio
n co
ncea
lmen
t. T
his
is a
sm
all t
rial
whi
ch m
ay b
e un
derp
ower
ed t
o de
tect
a d
iffer
ence
be
twee
n th
e ph
otos
ensi
tiser
s
Appendix 19
274
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
275Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Kah
aleh
et
al. (
2008
)133
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry U
SASt
udy
desi
gn
Non
-RC
TN
o. o
f pa
rtic
ipan
tsTo
tal:
48In
terv
entio
n: 1
9C
ompa
rato
r: 29
No.
of r
ecru
itin
g ce
ntre
s O
neFo
llow
-up
peri
od a
nd
freq
uenc
y FU
at
1 m
th a
nd e
very
3
mth
the
reaf
ter
(or
earl
ier
if th
ere
wer
e co
mpl
icat
ions
)
Trea
tmen
t in
tent
ion
Palli
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y N
on-r
esec
tabl
e ch
olan
gioc
arci
nom
aM
ain
elig
ibili
ty c
rite
ria
Unc
lear
, PD
T o
ffere
d af
ter
Dec
embe
r 20
04 t
o al
l pa
tient
s w
ith n
on-r
esec
tabl
e ch
olan
gioc
arci
nom
a or
re
sect
able
lesi
ons
deem
ed
inop
erab
lePa
tien
t ch
arac
teri
stic
s%
Mal
e: 50
Age
ran
ge: 2
6–94
yrM
ean
age:
66.6
yrTu
mou
r ex
tens
ion:
Bis
mut
h I,
6%; B
ism
uth
II, 1
9%;
Bism
uth
III, 3
5%; B
ism
uth
IV, 4
0%Fu
rthe
r pa
tient
ch
arac
teri
stic
s w
ere
repo
rted
Path
olog
ical
dia
gnos
is w
as
confi
rmed
in 6
9% o
f cas
esC
onco
mit
ant
trea
tmen
t Tw
enty
-tw
o pa
tient
s ha
d ch
emot
hera
py a
nd 1
9 ha
d ra
diot
hera
py. A
ll pa
tient
s re
ceiv
ed p
erip
roce
dure
an
tibio
tic p
roph
ylax
is
Tria
l tre
atm
ents
ER
CP
with
PD
T a
nd s
tent
vs
ERC
P w
ith S
tent
alo
neIn
terv
enti
on S
elec
tive
deco
mpr
essi
on o
f all
opac
ified
, dila
ted
segm
ents
was
att
empt
ed w
ith
boug
ie a
nd b
allo
on d
ilata
tion
to a
ssis
t in
the
pl
acem
ent
of p
olye
thyl
ene
sten
tsIn
trav
enou
s Ph
otof
rin
at 2
mg/
kg 4
8 hr
pri
or t
o 63
3-nm
(±
3-nm
) lig
ht fr
om a
200
0-m
W d
iode
la
ser,
deliv
ered
thr
ough
a 3
-m le
ngth
fibr
e ha
ving
a
2.5-
cm-lo
ng c
ylin
dric
al d
iffus
er a
t di
stal
end
(d
iffus
er w
as in
sert
ed in
to a
10F
she
ath
of a
pl
astic
ste
nt)
Phot
oact
ivat
ion
perf
orm
ed a
t 63
3 nm
* w
ith a
lig
ht d
ose
of 1
80 J/
cm2 ,
fluen
ce o
f 0.2
5 W/c
m2 a
nd
dura
tion
of 7
50 s.
One
or
two
segm
ents
tre
ated
at
dis
cret
ion
of e
ndos
copi
st. P
DT
rep
eate
d at
3-
mth
inte
rval
s w
hen
all s
tent
s w
ere
repl
aced
(t
his
was
don
e ea
rlie
r if
prem
atur
e oc
clus
ion
or
mig
ratio
n oc
curr
ed)
*Alth
ough
rep
orte
d as
620
nm
in t
he p
aper
, bas
ed
on t
he t
ype
of la
ser
used
thi
s ap
pear
s to
hav
e be
en a
typ
ogra
phic
err
orC
ompa
rato
r Se
lect
ive
deco
mpr
essi
on o
f all
opac
ified
, dila
ted
segm
ents
was
att
empt
ed w
ith
boug
ie a
nd b
allo
on d
ilata
tion
to a
ssis
t in
the
pl
acem
ent
of p
olye
thyl
ene
sten
ts (
7F, 8
.5F
and
10F
in d
iam
eter
). R
epea
ted
if in
dica
ted
until
pa
tient
ref
usal
or
deat
h
Mor
talit
y A
t en
d of
stu
dy 1
0 pa
tient
s w
ere
still
al
ive,
eig
ht b
eing
from
the
PD
T g
roup
The
re w
as s
tatis
tical
ly s
igni
fican
t pr
olon
ged
surv
ival
in t
he P
DT
gro
up (
mea
n 16
.2 m
th, S
D
2.4)
com
pare
d w
ith t
he S
tent
-alo
ne g
roup
(m
ean
7.4
mth
, SD
1.6
), p
< 0.
003.
Mor
talit
y ra
tes
wer
e si
gnifi
cant
ly lo
wer
in t
he P
DT
gro
up a
t 3
mth
(0%
vs
28%
, p =
0.0
1), a
nd 6
mth
(16
% v
s 52
%, p
= 0
.01)
, bu
t no
t at
12
mth
(56
% v
s 82
%, p
= 0
.08)
vs
Sten
t-al
one
grou
pM
orbi
dity
Bot
h gr
oups
had
sig
nific
antly
dec
reas
ed
leve
ls o
f ser
um b
iliru
bin
at 3
mth
whe
n co
mpa
red
to b
asel
ine
leve
ls (
p =
0.00
8 fo
r PD
T a
nd p
= 0
.000
1 fo
r st
ent
only
), al
thou
gh t
here
was
no
sign
ifica
nt
diffe
renc
e be
twee
n th
e tw
o gr
oups
in t
he d
egre
e of
dec
reas
e (p
= 0
.78)
QoL
and
ret
urn
to n
orm
al a
ctiv
ity
Not
as
sess
edA
Es
Sten
t-al
one
grou
p: 1
0 pa
tient
s de
velo
ped
chol
angi
tis (
with
tw
o pa
tient
s dy
ing
as a
co
nseq
uenc
e). F
our
patie
nts
deve
lope
d pa
ncre
atiti
s an
d on
e ha
d du
oden
al p
erfo
ratio
n. F
urth
er r
esul
ts
repo
rted
. PD
T g
roup
: thr
ee p
atie
nts
expe
rien
ced
skin
pho
toto
xici
ty. S
even
pat
ient
s de
velo
ped
chol
angi
tis, t
wo
deve
lope
d ch
olec
ystit
is, a
nd t
wo
haem
obili
a. Fu
rthe
r re
sults
rep
orte
dR
esou
rce
use
Not
ass
esse
d
Aut
hors
’ con
clus
ions
ER
CP
with
PD
T
seem
s to
incr
ease
su
rviv
al in
pat
ient
s w
ith u
nres
ecta
ble
chol
angi
ocar
cino
ma
whe
n co
mpa
red
with
ER
CP
alon
e, a
lthou
gh it
re
mai
ns t
o be
pro
ved
whe
ther
thi
s is
due
to
PDT
or
the
num
ber
or
ERC
P se
ssio
nsB
rief
stu
dy a
ppra
isal
T
he a
ims
of t
his
stud
y at
its
ince
ptio
n ar
e un
cert
ain
as t
he s
tudy
be
gan
in 2
001,
but
PD
T o
nly
beca
me
avai
labl
e fo
r us
e in
20
04. F
rom
thi
s po
int
on, P
DT
was
offe
red
to a
ll pa
tient
s, m
akin
g it
diffi
cult
to r
ecru
it gr
oups
with
sim
ilar
base
line
char
acte
rist
ics.
How
ever
, the
aut
hors
ac
know
ledg
ed t
hat
the
stud
y de
sign
pre
vent
ed
defin
itive
con
clus
ions
fr
om b
eing
dra
wn
F, T
he ‘F
renc
h si
ze’ o
f the
she
ath
used
to
intr
oduc
e a
sten
t.
Appendix 19
276 Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Ort
ner
et a
l. (20
03)13
4
Dat
a so
urce
Fu
ll pu
blis
hed
pape
rC
ount
ry
Ger
man
yLa
ngua
ge
Engl
ish
Stud
y de
sign
R
CT
No.
of
part
icip
ants
Tota
l: 39
Inte
rven
tion:
20
Com
para
tor:
19N
o. o
f re
crui
ting
ce
ntre
s Tw
oFo
llow
-up
peri
od a
nd
freq
uenc
y 14
d,
3 m
th, 6
mth
afte
r th
e in
terv
entio
n.
Surv
ivor
s th
en
follo
wed
up
at
6-m
th in
terv
als
Trea
tmen
t in
tent
ion
Palli
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y N
CC
Mai
n el
igib
ility
cri
teri
a In
clus
ion
crite
ria
wer
e pa
tient
s at
le
ast
18 yr
of a
ge w
ith a
pro
xim
al
mal
igna
nt t
umou
r of
the
bile
du
cts
(Bis
mut
h ty
pes
II–IV
, TN
M
stag
es II
I and
IV). T
hey
had
a la
rge
(> 3
cm in
dia
met
er),
imag
ing-
confi
rmed
, non
-res
ecta
ble
tum
our
(ass
esse
d by
tw
o in
depe
nden
t su
rgeo
ns),
posi
tive
hist
olog
y an
d no
evi
denc
e of
can
cer
of a
noth
er
orga
n. E
xclu
sion
cri
teri
a w
ere
porp
hyri
a, pr
evio
us c
hem
othe
rapy
or
rad
ioth
erap
y, pr
evio
us
tech
nica
lly s
ucce
ssfu
l ste
ntin
g (d
etai
ls in
pap
er),
inse
rtio
n of
a
met
al s
tent
, par
tial r
esec
tion
of
chol
angi
ocar
cino
ma,
diag
nost
ic
ERC
P m
ore
than
1 m
th p
revi
ously
an
d a
Kar
nofs
ky in
dex
of <
30%
. Fu
rthe
r de
tail
is p
rese
nted
in t
he
pape
rPa
tien
t ch
arac
teri
stic
s%
Mal
e: N
ot s
tate
dA
ge r
ange
: 53–
85M
edia
n ag
e: In
terv
entio
n 64
; co
ntro
l 68
(NS)
Can
cer
stag
e: St
age
III, s
even
; st
age
IVa,
19; s
tage
IVb
13Bi
smut
h ty
pe: I
I, tw
o; II
I, si
x; IV
, 31
100%
of a
ll ca
ses
wer
e hi
stol
ogic
ally
con
firm
edFu
rthe
r pa
tient
cha
ract
eris
tics
wer
e re
port
edC
onco
mit
ant
trea
tmen
t O
ral
cipr
oflox
acin
the
rapy
, 250
mg
twic
e da
ily, w
as s
tart
ed b
efor
e ER
CP
and
cont
inue
d fo
r 14
d
Tria
l tre
atm
ents
PD
T +
Dou
ble
sten
ting
vs St
entin
g al
one
Inte
rven
tion
See
com
para
tor
for
deta
ils o
f ste
ntin
g. PD
T p
atie
nts
rece
ived
Pho
tofr
in a
t a
dosa
ge o
f 2
mg/
kg b
ody
wt
intr
aven
ously
48
hr b
efor
e la
ser
activ
atio
n. E
ndop
rost
hese
s w
ere
rem
oved
and
an
end
osco
pic
Hui
breg
tse
Cot
ton
set
cath
eter
w
as in
trod
uced
pro
xim
ally
abo
ve t
he s
tric
ture
s. In
tral
umin
al p
hoto
activ
atio
n w
as p
erfo
rmed
with
a
lase
r qu
artz
fibr
e w
ith a
cyl
indr
ical
diff
user
tip
, len
gth
40 m
m, c
ore
diam
eter
400
µm
. Pho
toac
tivat
ion
was
pe
rfor
med
at
630
nm u
sing
a li
ght
dose
of 1
80 J/
cm2 ,
fluen
ce o
f 0.2
41 W
/cm
2 and
irra
diat
ion
time
of 7
50 s
unde
r a
cont
inuo
us s
alin
e pe
rfus
ion.
A n
ew s
et o
f en
dopr
osth
eses
was
inse
rted
afte
r co
mpl
etio
n of
PD
T. Fu
rthe
r te
chni
cal d
etai
ls o
f the
pro
cedu
re a
re
avai
labl
e in
the
pap
er. P
atie
nts
rem
aine
d in
a d
arke
ned
room
for
3–4
d af
ter
inje
ctio
n an
d th
erea
fter
patie
nts
wer
e gr
adua
lly a
dapt
ed t
o lig
ht. I
f any
FU
ex
amin
atio
n sh
owed
evi
denc
e of
tum
our
in t
he b
ile
duct
, PD
T w
as r
epea
ted.
Mea
n nu
mbe
r of
tre
atm
ents
w
as 2
.4 (
min
imum
1, m
axim
um 5
), th
e m
ean
no o
f ill
umin
atio
ns p
er p
atie
nt w
as 5
.3 a
nd t
he m
edia
n tr
eatm
ent
time
was
79
min
(m
inim
um 4
0; m
axim
um
180)
. All
patie
nts
rece
ived
oxyg
en v
ia a
nas
al c
athe
ter t
o op
timise
the
PDT
effe
ctC
ompa
rato
r En
dosc
opic
dou
ble-
sten
ting
follo
wed
dia
gnos
tic E
RC
P (a
ll pa
tient
s re
ceiv
ed
oral
cip
roflo
xaci
n th
erap
y 25
0 m
g tw
ice
daily
be
fore
ER
CP
and
cont
inue
d fo
r 14
d).
At
leas
t tw
o 10
F en
dopr
osth
eses
had
to
be p
lace
d ab
ove
the
mai
n st
rict
ures
in e
very
pat
ient
. End
osco
pic
plas
tic
endo
pros
thes
es o
r pe
rcut
aneo
us p
last
ic p
rost
hese
s w
ere
used
. Suc
cess
ful d
rain
age
afte
r te
chni
cally
su
cces
sful
ste
ntin
g (d
efini
tion
give
n in
pap
er)
was
de
fined
as
a de
crea
se in
bili
rubi
n le
vel >
50%
with
in
7 d
afte
r st
entin
g. W
hen
the
1st
proc
edur
e di
d no
t le
ad t
o te
chni
cally
suc
cess
ful s
tent
ing,
a 2n
d pr
oced
ure
was
per
form
ed. W
hen
the
2nd
proc
edur
e w
as n
ot s
atis
fact
ory,
perc
utan
eous
ste
ntin
g w
as
perf
orm
ed. P
atie
nts
wer
e ra
ndom
ised
onl
y af
ter
tech
nica
lly s
ucce
ssfu
l ste
ntin
g. St
ent
exch
ange
s w
ere
perf
orm
ed e
very
3 m
th. E
ight
pat
ient
s re
ceiv
ed
extr
a in
terv
entio
ns (
chem
othe
rapy
, fou
r; PD
T, th
ree;
im
mun
othe
rapy
, one
) as
a la
st r
esor
t tr
eatm
ent
Mor
talit
y M
edia
n su
rviv
al in
the
PD
T g
roup
was
493
d
(95%
CI 2
76 t
o 71
0) a
nd 9
8 d
in t
he S
tent
ing-
only
gro
up
(95%
CI 8
7 to
107
) p <
0.0
001.
RR
= 0
.21
(95%
CI 0
.12
to
0.35
). Tw
o pa
tient
s in
the
PD
T g
roup
wer
e st
ill a
live
at t
he
time
of e
valu
atio
n. t
he s
tudy
was
ter
min
ated
ear
ly d
ue t
o th
e su
peri
ority
of P
DT
Mor
bidi
ty S
ucce
ssfu
l dra
inag
e w
as a
chie
ved
in 2
1%
of p
atie
nts
in b
oth
grou
ps. A
fter
PDT
ser
um b
iliru
bin
reac
hed
low
er le
vels
rel
ativ
e to
bas
elin
e an
d st
entin
g (p
< 0
.01)
. Suc
cess
ful d
rain
age
was
obt
aine
d in
72%
Mea
n nu
mbe
r of
ste
nt e
xcha
nges
: PD
T g
roup
= 3
.8,
sten
ting
alon
e =
3.7
QoL
and
ret
urn
to n
orm
al a
ctiv
ity
The
Kar
nofs
ky
inde
x im
prov
ed a
fter
PDT
with
a m
edia
n 80
% s
core
(m
inim
um 5
0%, m
axim
um 1
00%
); m
ean
chan
ge fr
om
base
line
3.00
but
did
not
impr
ove
in t
he S
tent
ing-
alon
e gr
oup.
The
diff
eren
ce in
cha
nge
from
bas
elin
e be
twee
n th
e PD
T +
Sten
ting
grou
p an
d th
e St
entin
g-al
one
grou
p w
as
11.4
3 (9
5% C
I 2.9
2 to
19.
95, p
< 0
.01)
. Afte
r PD
T p
hysi
cal
func
tioni
ng (
p <
0.01
) an
d gl
obal
QoL
(p
< 0.
001)
impr
oved
in
the
PD
T g
roup
but
not
in t
he S
tent
ing-
alon
e gr
oup.
The
re
sults
of i
ndiv
idua
l fac
tors
rel
atin
g to
QoL
mea
sure
s ar
e lis
ted
in t
he p
aper
AE
s Bu
rden
of t
reat
men
t w
as lo
wer
in P
DT
vs
Sten
ting
alon
e (p
< 0
.001
). Ph
otos
ensi
tivity
was
rep
orte
d by
tw
o (1
0%)
of P
DT
pat
ient
s; al
l rea
ctio
ns w
ere
mild
and
re
solv
ed c
ompl
etel
y. A
ny c
hola
ngiti
s oc
curr
ing
duri
ng F
U
was
con
side
red
an A
E. T
here
wer
e th
ree
case
s in
the
PD
T
grou
p an
d se
ven
in t
he S
tent
ing-
alon
e gr
oup.
Sten
osis
pr
obab
ly r
elat
ed t
o th
erap
y w
as r
epor
ted
by t
wo
in t
he
PDT
gro
up a
nd z
ero
in t
he S
tent
ing-
alon
e gr
oup.
Fata
l ch
olan
gitis
, sep
sis
poss
ibly
rel
ated
to
ther
apy:
PDT
gro
up
two
of 1
8, S
tent
ing-
alon
e gr
oup
six
of 1
9T
he fo
llow
ing
wer
e ca
uses
of d
eath
pro
babl
y no
t re
late
d to
the
rapy
:Pu
lmon
ary
embo
lism
: PD
T g
roup
one
of 1
8, S
tent
ing
alon
e th
ree
of 1
9C
ache
xia:
PDT
gro
up o
ne o
f 18,
Ste
ntin
g on
e of
19
Car
diac
failu
re: o
ne o
f 18,
one
of 1
9, r
espe
ctiv
ely
Met
asta
ses:
12 o
f 18,
eig
ht o
f 19,
res
pect
ivel
yC
hron
ic r
enal
failu
re: o
ne o
f 18,
zer
o of
19,
res
pect
ivel
yR
esou
rce
use
Not
ass
esse
d
Aut
hors
’ co
nclu
sion
s PD
T a
dded
to
best
sup
port
ive
care
impr
oves
su
rviv
al a
nd Q
oL
in p
atie
nts
with
N
CC
. Pro
long
ed
surv
ival
tim
e w
as
not
asso
ciat
ed
with
a h
igh
rate
of
AEs
Bri
ef s
tudy
ap
prai
sal T
his
was
a w
ell-
cond
ucte
d an
d re
port
ed t
rial
, w
hich
was
hal
ted
earl
y du
e to
the
su
peri
ority
of t
he
PDT
tre
atm
ent
NC
C, n
on-r
esec
tabl
e ch
olan
gioc
arci
nom
a.
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
277Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Witz
igm
ann
et a
l. (2
006)
135
Dat
a so
urce
Ful
l pub
lishe
d pa
per
Cou
ntry
Ger
man
yLa
ngua
ge E
nglis
hSt
udy
desi
gn N
on-R
CT
No.
of p
arti
cipa
nts
Tota
l: 18
4 (1
91 if
incl
udin
g se
ven
patie
nts
not
anal
ysed
du
e to
mis
sing
FU
dat
a)In
terv
entio
n: 6
8C
ompa
rato
r: 56
2nd
Com
para
tor:
60N
o. o
f rec
ruit
ing
cent
res
Not
sta
ted
Follo
w-u
p pe
riod
and
fr
eque
ncy
Unc
lear
–
patie
nts
wer
e re
crui
ted
over
10
yr, w
hich
app
ears
to
be t
he F
U p
erio
d
Trea
tmen
t in
tent
ion
Cur
ativ
e pa
lliat
ive
Type
(s)
of c
ance
r an
d hi
stol
ogy
Hila
r ch
olan
gioc
arci
nom
aM
ain
elig
ibili
ty c
rite
ria
Not
sta
ted
Pati
ent
char
acte
rist
ics
% M
ale:
52A
ge r
ange
: 22–
91 yr
Tum
our
stag
e: Pa
tient
s fr
om
all s
tage
s, bu
t m
ostly
IB a
nd
IIA Tum
our
exte
nt: P
atie
nts
from
al
l Bis
mut
h ty
pes,
but
mos
tly
type
IV. A
ccor
ding
to
both
Bi
smut
h–C
orle
tte
and
UIC
C
clas
sific
atio
ns t
here
wer
e m
ore
adva
nced
tum
ours
in
the
pal
liativ
e tr
eatm
ent
grou
ps t
han
in t
he r
esec
tion
grou
p (p
< 0
.05)
. Fur
ther
pa
tient
cha
ract
eris
tics
wer
e re
port
edT
he n
umbe
r of
cas
es
confi
rmed
his
tolo
gica
lly w
as
not
clea
rly
repo
rted
Con
com
itan
t tr
eatm
ent
Che
mot
hera
py, r
adia
tion
ther
apy,
chem
orad
iatio
n an
d ir
idiu
m im
plan
ts w
ere
occa
sion
ally
use
d
Tria
l tre
atm
ents
PD
T +
sten
ting
vs S
tent
ing
alon
e vs
Res
ectio
nIn
terv
enti
on
PDT
+ st
entin
g: In
trav
enou
s Ph
otof
rin
at 2
mg/
kg w
ith
phot
oact
ivat
ion
afte
r 1–
4 d.
R
epea
ted
whe
n th
ere
was
evi
denc
e of
tum
our
prog
ress
ion.
Fur
ther
PD
T
para
met
ers
wer
e no
t re
port
ed. S
ee b
elow
for
sten
ting
Com
para
tor
Sten
ting:
At
leas
t tw
o 9F
or
11.5
F pl
astic
en
dopr
osth
eses
wer
e pl
aced
ab
ove
the
mai
n st
rict
ures
an
d ex
chan
ged
ever
y 3
mth
2nd
com
para
tor
Res
ectio
n: O
ne o
f rig
ht-
side
d he
mih
epat
ecto
my,
righ
t tr
iseg
men
tect
omy,
left
hem
ihep
atec
tom
y, hi
lar
rese
ctio
n al
one
or
liver
tra
nspl
anta
tion,
with
ad
ditio
nal t
ypes
of s
urge
ry
whe
n re
quire
d. N
eoad
juva
nt
PDT
and
bili
ary
drai
nage
als
o gi
ven
if re
quire
d
Mor
talit
y PD
T +
sten
ting
vs S
tent
ing
alon
e:1-
and
2-
yr s
urvi
val r
ates
wer
e 51
% a
nd 1
6% v
s 23
% a
nd 1
0%,
resp
ectiv
ely;
med
ian
surv
ival
tim
e 12
mth
vs
6.4
mth
(p
< 0
.01)
; 63(
93%
) vs
51(
91%
) pa
tient
s ha
d di
ed b
y th
e en
d of
the
stu
dy (
the
mai
n ca
uses
wer
e tu
mou
r pr
ogre
ssio
n an
d co
mpl
icat
ions
of c
hron
ic c
hola
ngiti
s).
Res
ectio
n: T
he 3
0- a
nd 6
0-da
y de
ath
rate
s w
ere
8.3%
and
11
.7%
, res
pect
ivel
y. M
ultip
le o
rgan
failu
re fr
om in
fect
ive
com
plic
atio
ns w
as t
he m
ost
com
mon
cau
se o
f dea
th.
Ove
rall
1-, 3
- an
d 5-
yr s
urvi
val r
ates
incl
udin
g po
st
op d
eath
s w
ere
73%
, 40%
and
27%
, res
pect
ivel
y, w
ith
a m
edia
n su
rviv
al o
f 23
mth
. Neo
adju
vant
PD
T b
efor
e re
sect
ion
resu
lted
in 1
-, 3-
and
5-y
r su
rviv
al r
ates
of 8
8%,
42%
and
42%
com
pare
d w
ith 6
6%, 2
8% a
nd 1
9% a
fter
surg
ery
alon
e (n
s). T
here
was
no
sign
ifica
nt d
iffer
ence
in
med
ian
surv
ival
tim
e be
twee
n th
e (R
1 an
d R
2) r
esec
tion
grou
p an
d th
e PD
T +
Sten
ting
grou
pM
orbi
dity
PD
T +
sten
ting
and
Sten
ting
alon
e: A
t 3
mth
, in
the
PD
T +
sten
ting
grou
p, th
ere
was
a s
igni
fican
t di
ffere
nce
in m
ean
bilir
ubin
leve
ls r
elat
ive
to b
asel
ine
(p <
0.0
01).
PDT
+ st
entin
g gr
oup
had
sign
ifica
ntly
low
er
leve
ls o
f bili
rubi
n th
an t
he S
tent
ing-
alon
e gr
oup
(4.1
mg/
dl
vs 7
.3 m
g/dl
, p <
0.0
5). S
ucce
ssfu
l dra
inag
e ac
hiev
ed in
75
% o
f pat
ient
s re
ceiv
ing
PDT
+ st
entin
g co
mpa
red
with
39
% r
ecei
ving
ste
ntin
g al
one.
Res
ectio
n: R
ecur
renc
e in
27
patie
nts
QoL
and
ret
urn
to n
orm
al a
ctiv
ity
At
3 m
th, m
edia
n pr
e-tr
eatm
ent
Kar
nofs
ky p
erfo
rman
ce s
tatu
s in
crea
sed
by 2
% fo
r PD
T +
Sten
ting
and
decr
ease
d by
8%
in
Sten
ting-
alon
e gr
oup
(p <
0.0
1)A
Es
PDT
+ st
entin
g/St
entin
g al
one:
The
re w
ere
no
proc
edur
e-re
late
d de
aths
. Eig
ht P
DT
pat
ient
s ha
d sk
in
toxi
city
(gr
ades
I an
d II)
. Bac
teri
al c
hola
ngiti
s se
en in
38
PDT
+ St
entin
g pa
tient
s an
d 32
Ste
ntin
g-al
one
patie
nts
(ns)
. Res
ectio
n: m
ajor
com
plic
atio
ns r
epor
ted
in 5
2% o
f pa
tient
s (3
7% r
equi
red
rela
paro
tom
y). T
he m
ost
com
mon
co
mpl
icat
ion
was
bile
leak
age
(eig
ht p
atie
nts)
Res
ourc
e us
e M
edia
n ho
spita
l sta
ys w
ere
65 d
for
PDT
+ st
entin
g, 44
d fo
r st
entin
g al
one,
and
48
d fo
r re
sect
ion
Aut
hors
’ con
clus
ions
O
nly
com
plet
e tu
mou
r re
sect
ion,
incl
udin
g he
patic
re
sect
ion,
ena
bles
long
-ter
m
surv
ival
for
patie
nts
with
hi
lar
chol
angi
ocar
cino
ma.
Palli
ativ
e PD
T +
Sten
ting
resu
lted
in lo
nger
sur
viva
l th
an s
tent
ing
alon
e an
d ha
s a
sim
ilar
surv
ival
tim
e co
mpa
red
with
inco
mpl
ete
R1
and
R2
rese
ctio
nB
rief
stu
dy a
ppra
isal
N
o fir
m c
oncl
usio
ns
can
be d
raw
n fr
om t
he
resu
lts o
f thi
s st
udy
for
seve
ral r
easo
ns. T
here
was
he
tero
gene
ity o
f tre
atm
ents
w
ithin
the
thr
ee g
roup
s (e
.g. s
ome
patie
nts
in
the
rese
ctio
n gr
oup
also
re
ceiv
ed n
eoad
juva
nt P
DT
). T
he g
roup
s w
ere
also
cl
inic
ally
het
erog
eneo
us
(sig
nific
antly
diff
eren
t at
bas
elin
e fo
r se
vera
l pa
ram
eter
s), a
nd t
here
was
w
ide
vari
atio
n in
leng
th o
f FU
bet
wee
n gr
oups
and
pa
tient
s
UIC
C, I
nter
natio
nal U
nion
Aga
inst
Can
cer.
Appendix 19
278
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
279
Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Zoe
pf e
t al.
(200
5)13
6
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry G
erm
any
Lang
uage
Eng
lish
Stud
y de
sign
RC
TN
o. o
f par
tici
pant
sTo
tal:
32In
terv
entio
n: 1
6C
ompa
rato
r: 16
No.
of r
ecru
itin
g ce
ntre
s N
ot s
tate
dFo
llow
-up
peri
od a
nd
freq
uenc
y 1,
3, 6
, 9, 1
2 an
d ev
ery
3 m
th. E
arlie
r en
dosc
opic
inte
rven
tions
w
ere
perf
orm
ed w
hen
need
ed in
cas
e of
clo
ttin
g or
dis
loca
tion
Trea
tmen
t in
tent
ion
Palli
ativ
eM
ain
elig
ibili
ty c
rite
ria
Adv
ance
d, n
on-r
esec
tabl
e BD
CPa
tien
t ch
arac
teri
stic
s%
Mal
e: 63
Med
ian
age:
68 yr
(ra
nge
52–8
0 yr
)C
ance
r st
age:
Stag
e II
+ ly
mph
no
des,
one;
sta
ge IV
, 31
Initi
al m
edia
n K
arno
fsky
pe
rfor
man
ce s
tatu
s: 90
%
(70–
100)
Ove
rall
63%
of c
ases
wer
e co
nfirm
ed h
isto
logi
cally
Con
com
itan
t tr
eatm
ent
All
patie
nts
rece
ived
pro
phyl
actic
an
tibio
tic t
reat
men
t be
fore
th
e pr
oced
ure
with
1 g
of
Cef
tria
xon,
giv
en in
trav
enou
sly
30 m
in b
efor
e in
terv
entio
n.
Ong
oing
ant
ibio
tic o
ral
trea
tmen
t w
ith c
hino
lone
was
gi
ven
for
a to
tal o
f 14
d. T
he
1st
eigh
t PD
T p
atie
nts
had
intr
aven
ous
Cef
riax
on o
ver
3 d
but
did
not
rece
ive
cont
inui
ng
oral
ant
ibio
tic t
reat
men
t
Tria
l tre
atm
ents
PD
T +
end
osco
pic
drai
nage
vs
Endo
scop
ic d
rain
age
alon
eIn
terv
enti
on P
hoto
san-
3 w
as g
iven
in
trav
enou
sly a
t a
dose
of 2
mg/
kg b
w
48 h
r be
fore
lase
r ir
radi
atio
n. A
flex
ible
cy
lindr
ical
diff
user
pro
be w
as u
sed.
The
pr
obe
was
mou
nted
on
a 40
0-µ
m q
uart
z fib
re w
ith a
n ac
tive
leng
th o
f 4cm
and
a
radi
opaq
ue m
arke
r at
the
dis
tal fi
bre
tip.
A d
iode
lase
r sy
stem
with
a m
axim
um
pow
er o
utpu
t of
2 W
and
a w
avel
engt
h of
633
± 3
nm
was
use
d as
ligh
t so
urce
. Ir
radi
atio
n tim
e w
as c
alcu
late
d fo
r a
light
en
ergy
den
sity
of 2
00 J/
cm2 .
In m
ost
case
s th
is w
as a
roun
d 55
0 s.
the
pow
er d
ensi
ty
was
450
–500
mW
/cm
and
ene
rgy
dose
w
as 2
50–2
75 J/
cm o
f diff
user
leng
th. F
or
tran
spap
illar
y PD
T t
he li
ght
appl
icat
or w
as
inse
rted
thr
ough
the
wor
king
cha
nnel
of
a du
oden
osco
pe. F
or p
ercu
tane
ous
PDT
th
e qu
artz
fibr
e w
as g
uide
d in
four
pat
ient
s th
roug
h th
e pa
rtia
lly r
emov
ed p
ercu
tane
ous
cath
eter
and
in o
ne p
atie
nt t
hrou
gh t
he
wor
king
cha
nnel
of a
cho
lang
iosc
ope.
T
he 1
st P
DT
ses
sion
was
per
form
ed a
t a
med
ian
of 4
.5 m
th (
1–9)
afte
r di
agno
sis
of
BDC
. Nin
e pa
tient
s re
ceiv
ed a
2nd
PD
T
sess
ion
afte
r 3–
9 m
th a
nd o
ne p
atie
nt a
3rd
se
ssio
n 6
mth
afte
r th
e 2n
d se
ssio
n. F
urth
er
PDT
par
amet
ers
wer
e no
t re
port
ed.
All
patie
nts
wer
e pr
ovid
ed w
ith p
last
ic
endo
pros
thes
es im
med
iate
ly a
fter
the
PDT
tr
eatm
ent
Com
para
tor T
he a
im o
f the
en
dopr
osth
etic
tre
atm
ent
was
bila
tera
l hila
r dr
aina
ge. E
ndop
rost
hese
s w
ere
regu
larl
y ch
ange
d ev
ery
3 m
th o
r ea
rlie
r in
cas
e of
cl
ottin
g or
dis
loca
tion
Mor
talit
y T
he P
DT
gro
up h
ad a
long
er
surv
ival
tim
e co
mpa
red
to t
he e
ndop
rost
hesi
s gr
oup
(21
mth
vs
7 m
th, p
= 0
.01)
. In
the
PDT
gr
oup,
30-d
mor
talit
y w
as 0
% a
nd 6
% in
the
en
dopr
osth
esis
gro
up. A
t th
e tim
e of
eva
luat
ion,
th
ree
patie
nts
in t
he P
DT
gro
up a
nd o
ne in
th
e en
dopr
osth
esis
gro
up w
ere
still
aliv
e. T
he
PDT
pat
ient
s w
ere
deem
ed t
o be
in g
ood
clin
ical
con
ditio
n w
ithou
t si
gnifi
cant
cho
lest
asis
. N
o de
tails
wer
e pr
ovid
ed o
n th
e su
rviv
or in
th
e en
dopr
osth
esis
gro
up. I
n th
e PD
T g
roup
12
pat
ient
s di
ed o
f tum
our-
rela
ted
caus
es,
and
one
patie
nt o
f a p
erfo
rate
d ga
stri
c ul
cer.
Cau
ses
of d
eath
wer
e no
t re
port
ed fo
r th
e en
dopr
osth
esis
gro
upM
orbi
dity
4 w
k af
ter
initi
al P
DT,
mos
t PD
T p
atie
nts
show
ed a
n al
mos
t co
mpl
ete
elim
inat
ion
of b
ile d
uct
sten
osis
in t
he t
reat
ed
area
as
show
n w
ith c
hola
ngio
grap
hy (
data
no
t pr
ovid
ed).
Med
ian
bilir
ubin
leve
l afte
r 1s
t in
terv
entio
n w
as n
ot s
igni
fican
tly d
iffer
ent
betw
een
the
grou
psQ
oL a
nd r
etur
n to
nor
mal
act
ivit
y Q
oL
as a
sses
sed
by t
he K
arno
fsky
sca
le d
id n
ot
sign
ifica
ntly
impr
ove
afte
r PD
TA
Es T
hree
pat
ient
s de
velo
ped
an in
fect
ed
bilio
ma
with
pro
long
ed c
hola
ngiti
s af
ter
PDT
tre
atm
ent,
whi
ch c
ould
be
man
aged
by
ant
ibio
tic t
reat
men
t. A
noth
er p
atie
nt
deve
lope
d ch
olec
ystit
is 2
mth
afte
r a
2nd
trea
tmen
t se
ssio
n, w
hich
led
to s
urgi
cal
lapa
rosc
opic
cho
lecy
stec
tom
y. T
here
was
no
skin
pho
toto
xici
ty o
bser
ved
in a
ny o
f the
th
ree
patie
nts.
One
pat
ient
dev
elop
ed s
ever
e ba
cter
ial c
hola
ngiti
s du
ring
end
opro
sthe
tic
ther
apy,
whi
ch w
as s
ucce
ssfu
lly t
reat
ed b
y st
anda
rd a
ntib
iotic
the
rapy
Res
ourc
e us
e N
ot a
sses
sed
Aut
hors
’ co
nclu
sion
s PD
T is
min
imal
ly
inva
sive
but
the
re
is a
con
side
rabl
e ri
sk o
f cho
lang
itis
afte
r th
e pr
oced
ure.
PD
T w
as fo
und
to
resu
lt in
a s
ubst
antia
l pr
olon
gatio
n of
su
rviv
al t
ime
but
this
wou
ld n
eed
confi
rmat
ion
in
furt
her
patie
nt
seri
es. P
DT
has
the
po
tent
ial t
o re
sult
in a
ch
ange
over
of c
urre
nt
palli
ativ
e tr
eatm
ent
of B
DC
Bri
ef s
tudy
ap
prai
sal A
sm
all t
rial
with
cl
ear
repo
rtin
g of
pr
oced
ures
. The
re
sults
app
ear
to b
e re
liabl
e bu
t w
ould
ne
ed c
onfir
mat
ion
in
a la
rger
tri
al
Appendix 19
278
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
279
Appendix 20 Brain cancer data extraction
Appendix 20
280 Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Elja
mel
et
al. (
2008
)139
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry U
KLa
ngua
ge E
nglis
hSt
udy
desi
gn
RC
TN
o. o
f pa
rtic
ipan
tsTo
tal:
27 a
naly
sed
(42
rand
omis
ed?)
Inte
rven
tion:
13
Com
para
tor:
14N
o. o
f rec
ruit
ing
cent
res
One
Follo
w-u
p pe
riod
an
d fr
eque
ncy
3-m
onth
ly, u
ntil
deat
h
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y G
BMM
ain
Elig
ibili
ty
Cri
teri
aPa
tient
s ov
er 1
7 yr
, w
ith a
new
MR
I di
agno
sis
of G
BM a
nd
a K
arno
fsky
sco
re
≥ 60
Pati
ent
char
acte
rist
ics
% M
ale:
67M
ean
age:
59.8
yrM
ean
Kar
nofs
ky
perf
orm
ance
sco
re:
70 Con
com
itan
t tr
eatm
ent
Som
e st
udy
patie
nts
rece
ived
add
ition
al
trea
tmen
ts s
uch
as c
hem
othe
rapy
an
d fu
rthe
r su
rger
y. H
owev
er, t
here
w
ere
no s
tatis
tical
ly
sign
ifica
nt d
iffer
ence
s be
twee
n th
e gr
oups
in
pat
ient
s re
ceiv
ing
addi
tiona
l tre
atm
ents
Tria
l tre
atm
ents
Flu
ores
cenc
e-gu
ided
re
sect
ion
and
repe
titiv
e PD
T a
nd
radi
othe
rapy
vs
stan
dard
res
ectio
n an
d ra
diot
hera
pyIn
terv
enti
on P
DT:
Pat
ient
s w
ere
give
n 2
mg/
kg P
hoto
frin
intr
aven
ously
48
h be
fore
sur
gery
, and
20
mg/
kg A
LA o
rally
3
h be
fore
sur
gery
. Afte
r re
mov
al o
f bul
k of
tum
our
viol
et-b
lue
light
(37
5–44
0 nm
) w
ith a
440
-nm
obs
erva
tion
filte
r w
as u
sed
to il
lum
inat
e th
e ca
vity
with
fluo
resc
ence
de
tect
ed b
y a
high
-qua
lity
phot
odia
gnos
is
cam
era,
and
dete
cted
tum
our
was
rem
oved
un
til n
o fu
rthe
r flu
ores
cenc
e w
as d
etec
ted.
A
lase
r-ba
sed
(405
nm
) pr
otop
orph
yrin
-IX
spec
tros
copy
det
ectio
n sy
stem
was
use
d to
det
ect
any
rem
aini
ng t
umou
r ce
lls a
t th
e m
argi
ns, w
hich
wer
e re
mov
ed. A
siz
e-10
bal
loon
cat
hete
r w
as in
flate
d to
fit
the
cavi
ty w
ith 0
.8%
intr
alip
id s
olut
ion.
Afte
r th
e pa
tient
aw
oke
from
sur
gery
the
1st
PD
T t
reat
men
t, us
ing
630-
nm d
iode
lase
r (6
00 m
W),
was
giv
en in
the
atre
rec
over
y at
100
J/cm
2 ; m
ore
PDT
was
giv
en a
t 72
, 96
, 120
and
144
hr.
Patie
nts
also
rec
eive
d st
anda
rd r
adio
ther
apy.
Adv
ice
was
giv
en o
n su
n pr
otec
tion
mea
sure
sC
ompa
rato
r Tum
our
rem
oval
usi
ng
the
sam
e ne
uron
avig
atio
n an
d su
rgic
al
mic
rosc
ope
as t
he P
DT
gro
up. P
atie
nts
also
re
ceiv
ed s
tand
ard
radi
othe
rapy
Mor
talit
y M
ean
surv
ival
in t
he P
DT
gro
up
was
52.
8 w
k vs
24.
2 w
k in
the
sur
gery
gr
oup
(p <
0.0
01)
Mor
bidi
ty T
here
was
no
resi
dual
tum
our
on d
isch
arge
sca
n in
10/
13 P
DT
pat
ient
s vs
4/
14 s
urge
ry p
atie
nts.
Mea
n tim
e to
tum
our
prog
ress
ion
was
8.6
mth
in t
he P
DT
gro
up
vs 4
.8 m
th in
the
sur
gery
gro
up (
p <
0.01
)Q
oL a
nd r
etur
n to
nor
mal
act
ivit
y T
he
Kar
nofs
ky s
core
at
6 m
th h
ad im
prov
ed
from
70
(at
base
line)
to
80 in
the
PD
T
grou
p, al
thou
gh t
he a
utho
rs r
epor
ted
an
impr
ovem
ent
of 2
0 po
ints
. The
sco
res
rem
aine
d th
e sa
me
for
the
surg
ery
grou
p (a
t 70
)A
Es T
hree
pat
ient
s ha
d de
ep v
ein
thro
mbo
sis,
two
of w
hich
wer
e in
the
PD
T
grou
p. N
o in
fect
ions
or
seiz
ures
occ
urre
dR
esou
rce
use
The
re w
as n
o di
ffere
nce
betw
een
the
grou
ps in
leng
th o
f hos
pita
l st
ay (
both
had
a m
ean
stay
of 7
d)
Aut
hors
’ con
clus
ions
ALA
and
Pho
tofr
in
fluor
esce
nce-
guid
ed r
esec
tion
with
re
petit
ive
PDT
offe
r a
wor
thw
hile
sur
viva
l ad
vant
age,
with
out
adde
d ri
sk, t
o pa
tient
s w
ith G
BMB
rief
stu
dy a
ppra
isal
The
Kar
nofs
ky
resu
lts w
ere
repo
rted
inco
nsis
tent
ly w
ithin
th
e pa
per,
mak
ing
inte
rpre
tatio
n di
fficu
lt.
It w
as u
ncle
ar h
ow m
any
patie
nts
had
actu
ally
bee
n ra
ndom
ised
and
tre
ated
, as
14
patie
nts
with
neg
ativ
e bi
opsy
res
ults
wer
e su
bseq
uent
ly e
xclu
ded
from
ana
lyse
s. T
he
anal
ysed
pop
ulat
ion
does
not
the
refo
re
appe
ar t
o re
flect
the
pop
ulat
ion
pres
entin
g cl
inic
ally
(pa
tient
s w
ith a
n M
RI d
iagn
osis
). A
lthou
gh t
he s
tudy
mad
e us
e of
blin
ding
to
ass
ess
outc
omes
, it
was
nev
erth
eles
s un
clea
r w
heth
er s
uita
ble
met
hods
had
bee
n us
ed t
o ra
ndom
ise
and
allo
cate
par
ticip
ants
to
tre
atm
ents
. No
resu
lts w
ere
repo
rted
on
pos
sibl
e ph
otos
ensi
tisat
ion
effe
cts.
The
au
thor
s di
d th
ough
ack
now
ledg
e th
e ne
ed
for
a m
uch
larg
er s
tudy
GBM
, glio
blas
tom
a m
ultif
orm
e; M
RI,
mag
netic
res
onan
ce im
agin
g.
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
281Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
K
rish
nam
urth
y et
al.
(200
0)13
8
Dat
a so
urce
Ful
l pu
blis
hed
pape
rC
ount
ry U
SALa
ngua
ge E
nglis
hSt
udy
desi
gn
Non
-RC
TN
o. o
f pa
rtic
ipan
tsTo
tal:
18In
terv
entio
n: S
ixC
ompa
rato
r: Si
x2n
d C
ompa
rato
r: Si
xN
o. o
f rec
ruit
ing
cent
res
One
Follo
w-u
p pe
riod
an
d fr
eque
ncy
Day
s 1
and
2, a
t di
scha
rge
from
ho
spita
l, at
1, 4
and
6
wk,
then
at
3-m
th
inte
rval
s
Trea
tmen
t in
tent
ion
Cur
ativ
e Pa
lliat
ive
Type
(s)
of c
ance
r an
d hi
stol
ogy
12 g
liobl
asto
ma,
five
anap
last
ic
astr
ocyt
oma,
one
mal
igna
nt
epen
dym
oma
Mai
n el
igib
ility
cri
teri
a Pa
tient
s ag
ed 1
8–75
yr, w
ith s
upra
tent
oria
l pr
imar
y m
alig
nant
bra
in t
umou
rs
≤ 5
cm in
dia
met
er, a
Kar
nofs
ky
ratin
g ≥
60, a
nd w
ho h
ad r
ecur
rent
or
res
idua
l tum
ours
wer
e el
igib
le.
Patie
nts
had
to h
ave
rece
ived
ra
diat
ion
ther
apy
> 3
mth
pri
or t
o PD
T t
reat
men
t. Fu
rthe
r el
igib
ility
cr
iteri
a w
ere
repo
rted
Pati
ent
char
acte
rist
ics
Age
ran
ge: 3
2–70
yrM
edia
n K
arno
fsky
sco
re: 9
0Tu
mou
r lo
catio
ns a
lso
repo
rted
. All
patie
nts
had
initi
al s
urge
ry, r
adia
tion
ther
apy
and
chem
othe
rapy
bef
ore
recu
rren
ceC
onco
mit
ant
trea
tmen
t St
eroi
d th
erap
y if
requ
ired
Tria
l tre
atm
ents
PD
T 1
500–
3700
J vs
PD
T 3
700–
4400
J vs
PD
T 4
400–
5900
JIn
terv
enti
on P
DT
150
0–37
00 J
(gro
up 1
): In
trav
enou
s Ph
otof
rin
at 2
mg/
kg, f
ollo
wed
24
hr la
ter
by a
naes
thet
ic a
nd C
T o
r M
RI
scan
whi
ch lo
cate
s tu
mou
r us
ing
ster
eota
ctic
arc
sys
tem
. Six
opt
ical
di
ffusi
on t
ip fi
bres
(1.
6 m
m)
and
cent
ral fi
bre
inse
rted
thr
ough
dri
ll ho
les
into
sku
ll. R
ed li
ght
(630
nm
) fr
om a
n ar
gon
pum
ped-
dye
lase
r w
as
deliv
ered
thr
ough
opt
ical
fibr
es a
nd
beam
spl
itter
s to
indi
vidu
al d
iffus
ion
tip fi
bres
. Tum
ours
wer
e bi
opsi
ed
(and
if n
o m
alig
nanc
y w
as fo
und
the
patie
nt w
as e
xclu
ded
from
the
stu
dy).
Patie
nts
wer
e ad
vise
d ab
out
sunl
ight
pr
otec
tion,
and
abo
ut a
void
ing
dire
ct
sunl
ight
and
bri
ght
artifi
cial
ligh
t fo
r 6
wk
Com
para
tor
PDT
370
0–44
00 J
(gro
up 2
): Se
e ab
ove
2nd
com
para
tor
PDT
440
0–59
00 J
(gro
up 3
): Se
e ab
ove
Mor
talit
y M
ean
surv
ival
tim
e w
as
314
d (s
d =
106)
in g
roup
2 v
s 23
8 d
in
grou
p 3
(sd
= 61
). G
roup
1 n
ot s
tate
dM
orbi
dity
16
patie
nts
had
recu
rren
ce a
fter
PDT
(fo
ur in
gro
up
1, s
ix in
gro
up 2
and
six
in g
roup
3),
and
two
did
not.
Tim
e to
tum
our
recu
rren
ce w
as a
mea
n of
150
d in
gr
oup
2 vs
131
d in
gro
up 3
. Gro
up 1
no
t st
ated
QoL
and
ret
urn
to n
orm
al
acti
vity
Med
ian
Kar
nofs
ky r
atin
g ch
ange
d fr
om 9
0 (p
re-P
DT
) to
85
(pos
t PD
T)
AE
s Fi
ve p
atie
nts
had
post
oper
ativ
e pe
rman
ent
neur
olog
ical
def
ects
(ze
ro
in g
roup
1, t
wo
in g
roup
2, a
nd t
hree
in
gro
up 3
)R
esou
rce
use
Not
ass
esse
d
Aut
hors
’ con
clus
ions
Incr
easi
ng
the
light
dos
e in
crea
ses
the
odds
of
havi
ng p
erm
anen
t ne
urol
ogic
al d
efici
t, bu
t do
es n
ot in
crea
se s
urvi
val t
ime,
or
tim
e to
tum
our
prog
ress
ion.
The
re
was
no
diffe
renc
e in
rec
urre
nce
with
in
crea
sing
ligh
t do
seB
rief
stu
dy a
ppra
isal
Thi
s no
n-ra
ndom
ised
stu
dy a
ppea
red
to h
ave
far
too
smal
l a s
ampl
e si
ze t
o pr
ovid
e cl
inic
ally
mea
ning
ful r
esul
ts. R
esul
ts
wer
e no
t al
way
s pr
ovid
ed fo
r al
l thr
ee
grou
ps
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
283
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
283
Appendix 21 Head and neck cancer data extraction
Appendix 21
284
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
285Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Li e
t al
. (20
06)14
1
Dat
a so
urce
Fu
ll pu
blis
hed
pape
rC
ount
ry C
hina
Lang
uage
En
glis
hSt
udy
desi
gn
RC
TN
o. o
f pa
rtic
ipan
tsTo
tal:
30In
terv
entio
n: 1
5C
ompa
rato
r: 15
No.
of
recr
uiti
ng
cent
res
Not
st
ated
Follo
w-u
p pe
riod
and
fr
eque
ncy
FU
at 1
, 3 a
nd 6
m
th
Trea
tmen
t in
tent
ion
Not
sta
ted,
ap
pear
s pa
lliat
ive
Type
(s)
of c
ance
r an
d hi
stol
ogy
Nas
opha
ryng
eal
carc
inom
aM
ain
elig
ibili
ty
crit
eria
Pat
ient
s w
ho h
ad r
elap
sed
and
who
had
faile
d ra
diot
hera
pyPa
tien
t ch
arac
teri
stic
s%
Mal
e: 80
Age
ran
ge: 2
8–72
Mea
n ag
e: 54
yrC
ance
r st
age:
All
stag
e IV
and
had
loca
l re
laps
e. A
ll ha
d pr
ior
(faile
d) r
adio
ther
apy;
som
e al
so h
ad p
rior
ch
emot
hera
py,
6–12
mth
bef
ore
tria
l tr
eatm
ent
Con
com
itan
t tr
eatm
ent
Ant
i-vo
miti
ng t
reat
men
t fo
r ch
emot
hera
py
grou
p. C
hine
se h
erbs
(u
nspe
cifie
d)
Tria
l tre
atm
ents
PD
T v
s C
hem
othe
rapy
(c
ispl
atin
and
5-F
U)
Inte
rven
tion
Intr
aven
ous
Phot
ofri
n of
2
mg/
kg. L
ocal
ana
esth
etic
(lid
ocai
ne)
befo
re
light
(63
0 nm
) at
200
–300
J/cm
from
a d
iode
la
ser
thro
ugh
a cy
lindr
ical
diff
user
(1–
5 cm
) 48
hr
afte
r in
ject
ion.
Lig
ht w
as a
pplie
d to
on
e to
thr
ee o
verl
appi
ng s
egm
ents
for
12 m
in p
er s
egm
ent.
Segm
ents
had
at
leas
t a
0.5-
cm m
argi
n be
yond
the
lesi
on. A
fter
48-h
r ne
crot
ic t
issu
e re
mov
ed b
y bi
opsy
forc
eps
and
new
ly e
xpos
ed le
sion
s w
ere
re-t
reat
ed
afte
r cl
eani
ng. C
lean
ing
was
rep
eate
d w
hen
nece
ssar
y. Pa
tient
s as
ked
to a
void
sun
light
fo
r 4–
6 w
k af
ter
trea
tmen
t. M
axim
um
num
ber
of s
essi
ons
was
not
sta
ted
Com
para
tor
Cis
plat
in 8
0 m
g/m
2 and
5-F
U
500
mg/
m2 ,
both
div
ided
into
five
. Eac
h cy
cle
last
ed 4
wk.
Two
cycl
es w
ere
give
n
Mor
talit
y N
ot a
sses
sed
Mor
bidi
ty O
vera
ll cl
inic
al r
espo
nse
was
st
atis
tical
ly s
igni
fican
tly b
ette
r w
ith P
DT
th
an c
hem
othe
rapy
(p
= 0.
001)
. No
patie
nts
achi
eved
CR
. The
PD
T g
roup
had
mor
e pa
tient
s w
ith a
sig
nific
ant
resp
onse
(i.e
. 50
% r
educ
tion
for
1 m
th, 1
2 vs
2).
In t
hose
pa
tient
s w
ith n
asal
obs
truc
tions
PD
T
prod
uced
mor
e ef
fect
ive
debu
lkin
g (p
= 0
.04)
(s
ubgr
oup
of 1
6 pa
tient
s, 7/
8 im
prov
ed v
s 2/
8)Q
oL a
nd r
etur
n to
nor
mal
act
ivit
y PD
T
grou
p ha
d a
stat
istic
ally
sig
nific
ant
grea
ter
impr
ovem
ent
in K
arno
fsky
sco
re (
p =
0.02
). PD
T g
roup
incr
ease
d fr
om 4
5 to
70
vs
chem
othe
rapy
gro
up in
crea
sed
from
40
to
50 AE
s All
PDT
rel
ated
adv
erse
effe
cts
and
reac
tions
wer
e to
lera
ble.
Tre
atm
ent
to
the
lary
ngop
hary
nx a
rea
resu
lted
in s
light
pa
in a
nd in
crea
sed
nasa
l cav
ity s
ecre
tion
– re
solv
ed in
3–5
dO
ne c
ase
of s
ever
e la
ryng
opha
rynx
sw
ellin
g an
d pa
in. R
esol
ved
with
tre
atm
ent
1 w
k la
ter,
may
be
rela
ted
to li
ght
expo
sure
One
cas
e of
pho
tose
nsiti
vity
der
mat
itis
afte
r ac
cide
ntal
exp
osur
e to
day
light
. Res
olve
d af
ter
trea
tmen
t, 1
wk
late
rO
ne c
ase
of s
kin
pigm
enta
tion,
no
trea
tmen
t re
quire
d
Aut
hors
’ con
clus
ions
PD
T is
effe
ctiv
e an
d sa
fe fo
r th
e tr
eatm
ent
of a
dvan
ced
nasa
l ph
aryn
geal
can
cer
and
the
man
agem
ent
of
nasa
l obs
truc
tion
Bri
ef s
tudy
app
rais
al T
his
smal
l pilo
t st
udy
prov
ided
no
deta
ils o
n ra
ndom
isat
ion,
bl
indi
ng a
nd o
ther
stu
dy q
ualit
y pa
ram
eter
s ra
isin
g qu
estio
ns a
bout
the
val
idity
of
the
resu
lts. T
reat
men
t de
tails
wer
e w
ell
desc
ribe
d. It
doe
s no
t ap
pear
to
have
led
on
to a
larg
er s
tudy
, tho
ugh
the
auth
ors
righ
tly
stat
ed t
hat
furt
her
inve
stig
atio
n w
as n
eede
d
Appendix 21
284
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
285
Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Lou
katc
h et
al.
(199
5)14
2
Dat
a so
urce
Abs
trac
tC
ount
ry U
krai
neLa
ngua
ge E
nglis
hSt
udy
desi
gn N
on-R
CT
No.
of p
arti
cipa
nts
Tota
l: 14
5In
terv
entio
n: 4
2C
ompa
rato
r: 51
2nd
Com
para
tor:
52N
o. o
f rec
ruit
ing
cent
res
Not
sta
ted
Follo
w-u
p pe
riod
and
fr
eque
ncy
3 yr
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
Can
cer
and
His
tolo
gyPl
anoc
ellu
lar
canc
er o
f lar
ynx
Mai
n el
igib
ility
cri
teri
a N
ot
stat
edPa
tien
t ch
arac
teri
stic
s C
ance
r st
age:
Stag
e Ib
, 79;
sta
ge II
a, 66
. All
canc
ers
wer
e of
mid
dle
loca
lisat
ion.
N
o fu
rthe
r ch
arac
teri
stic
s w
ere
repo
rted
Con
com
itan
t tr
eatm
ent
Not
st
ated
Tria
l tre
atm
ents
Sur
gery
/in
trao
pera
tive
PDT
vs
Surg
ery/
intr
aope
rativ
e PD
T w
ithou
t la
ser
vs S
urge
ry a
lone
Inte
rven
tion
Cor
dect
omy
with
lo
cal a
naes
thet
ic, f
ollo
wed
by
adm
inis
trat
ion
of 0
.4%
sol
utio
n of
m
ethy
lene
blu
e ph
otos
ensi
tiser
. A
He-
Ne
lase
r of
wav
elen
gth
633
nm e
mitt
ing
at 2
5–30
mW
/cm
2 fo
r 5
min
was
use
d. F
urth
er P
DT
pa
ram
eter
s w
ere
not
repo
rted
Com
para
tor
Cor
dect
omy
with
lo
cal a
naes
thet
ic fo
llow
ed b
y la
ser
only
(sa
me
para
met
ers
as P
DT
gr
oup)
2nd
com
para
tor
Cor
dect
omy
with
loca
l ana
esth
etic
onl
y
Mor
bidi
ty A
fter
3 yr
the
re w
as
recu
rren
ce in
one
pat
ient
(2%
) an
d no
cas
es o
f met
asta
sis
in t
he P
DT
gr
oup,
four
cas
es o
f rec
urre
nce
(8%
) in
the
lase
r gr
oup
and
one
case
of m
etas
tasi
s, an
d fiv
e ca
ses
of r
ecur
renc
e (1
0%)
and
two
case
s of
met
asta
sis
in t
he S
urge
ry-a
lone
gr
oup
QoL
and
ret
urn
to n
orm
al
acti
vity
Not
ass
esse
dA
Es
PDT
gro
up: S
ome
patie
nts
had
oede
ma
of la
ryng
eal m
ucou
s m
embr
ane
and
one
patie
nt h
ad a
sm
all h
aem
orrh
age.
Sur
gery
-alo
ne
grou
p: O
ne p
atie
nt h
ad a
sm
all
haem
orrh
age.
Bot
h ha
emor
rhag
es
wer
e m
anag
ed b
y co
nser
vativ
e tr
eatm
ent
Aut
hors
’ con
clus
ions
In
trao
pera
tive
PDT
in p
atie
nts
with
sta
ges
I and
II la
ryng
eal c
ance
r co
uld
be e
ffect
ive
for
prev
entin
g re
curr
ence
and
met
asta
sis
of
tum
ours
Bri
ef s
tudy
app
rais
al T
his
stud
y us
ed c
ompa
rato
r tr
eatm
ents
suc
h th
at t
he r
esul
ts o
ffer
little
insi
ght
to h
ow P
DT
com
pare
s to
oth
er
trea
tmen
ts a
djun
ctiv
e to
sur
gery
. T
he s
tudy
als
o ex
amin
ed fe
w
outc
omes
and
the
re w
as s
pars
e re
port
ing
of m
etho
ds, p
atie
nt
char
acte
rist
ics
and
resu
lts
Appendix 21
286 Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Lo
ukat
ch e
t al.
(199
6)14
3
Dat
a so
urce
A
bstr
act
Cou
ntry
U
krai
neLa
ngua
ge
Engl
ish
Stud
y de
sign
N
on-R
CT
No.
of
part
icip
ants
Tota
l: 49
Inte
rven
tion:
19
Com
para
tor:
152n
d C
ompa
rato
r: 15
No.
of
recr
uiti
ng
cent
res
Not
st
ated
Follo
w-u
p pe
riod
and
fr
eque
ncy
3 yr
Trea
tmen
t in
tent
ion
Cur
ativ
eTy
pe(s
) of
can
cer
and
hist
olog
y SC
C in
la
ryng
eal p
art
of p
hary
nxM
ain
elig
ibili
ty c
rite
ria
Not
sta
ted
Pati
ent
char
acte
rist
ics
Can
cer
stag
e: St
age
II, 2
5;
stag
es II
I and
IV, 2
4N
o fu
rthe
r ch
arac
teri
stic
s w
ere
repo
rted
Con
com
itan
t tr
eatm
ent P
hary
ngot
omy
for
stag
e II
patie
nts
and
hem
ilary
ngop
hary
ngot
omy
for
stag
e III
–IV
pat
ient
s w
ith g
ener
al a
naes
thet
ic.
Post
oper
ativ
e co
balt
ther
apy
(45-
Gy
dose
). N
eck
diss
ectio
n op
erat
ion
for
patie
nts
deve
lopi
ng
met
asta
ses
Tria
l tre
atm
ents
PD
T v
s PD
T w
ith L
aser
onl
y vs
PD
T
with
Pho
tose
nsiti
ser
only
Inte
rven
tion
PD
T w
ith
met
hyle
ne b
lue
(inje
cted
lo
cally
) as
pho
tose
nsiti
ser,
follo
wed
by
633-
nm li
ght
for
5 m
in fr
om a
He-
Ne
lase
r at
25–
30 m
W/c
m2 .
Furt
her
PDT
par
amet
ers
wer
e no
t re
port
edC
ompa
rato
r As
for
PDT
gro
up b
ut w
ithou
t ph
otos
ensi
tiser
2nd
com
para
tor
As
for
PDT
gro
up b
ut w
ithou
t la
ser
Mor
talit
y2-
yr s
urviv
alPD
T g
roup
, 100
% (
stag
e II)
, 89%
(st
ages
III a
nd IV
); La
ser-
only
gro
up: 8
8% (
stag
e II)
, 86%
(st
ages
III a
nd
IV);
Phot
osen
sitis
er-o
nly
grou
p: 7
1% (
stag
e II)
, 75%
(s
tage
s III
and
IV)
3-yr
sur
vival
PDT
gro
up, 1
00%
(st
age
II), 6
7% (
stag
es II
I and
IV
); La
ser-
only
gro
up: 4
3% (
stag
es II
I and
IV);
Phot
osen
sitis
er-o
nly
grou
p: 3
8% (
stag
es II
I and
IV).
Stag
e II
resu
lts n
ot a
vaila
ble
for
last
tw
o gr
oups
Mor
bidi
ty A
fter
1 ye
ar, n
one
of t
he s
tage
II p
atie
nts
had
recu
rren
ce o
r m
etas
tasi
s. Fo
r st
age
III a
nd s
tage
IV
pat
ient
s, th
ere
was
rec
urre
nce
in o
ne p
atie
nt
(11%
) in
the
PD
T g
roup
, tw
o pa
tient
s (2
9%)
in t
he
Lase
r-on
ly g
roup
and
tw
o pa
tient
s (2
5%)
in t
he
Phot
osen
sitis
er-o
nly
grou
pA
fter
2 yr
, in
the
PDT
gro
up: r
ecur
renc
e in
10%
(st
age
II) a
nd 1
1% (
stag
es II
I and
IV);
in t
he L
aser
-onl
y gr
oup:
re
curr
ence
in 2
5% (
stag
e II)
, and
43%
(st
ages
III a
nd
IV);
in t
he P
hoto
sens
itise
r-on
ly g
roup
: rec
urre
nce
in
43%
(st
age
II), a
nd 5
0% (
stag
es II
I and
IV)
Dur
ing
the
3-yr
per
iod
ther
e w
ere
regi
onal
m
etas
tase
s in
0%
of P
DT
gro
up (
stag
e II)
, 11%
in
PDT
(st
ages
III a
nd IV
), 13
% o
f Las
er-o
nly
grou
p (s
tage
II),
14%
Las
er-o
nly
(sta
ges
III a
nd IV
), 14
%
Phot
osen
sitis
er-o
nly
(sta
ge II
), 25
% P
hoto
sens
itise
r-on
ly (
stag
es II
I and
IV)
QoL
and
ret
urn
to n
orm
al a
ctiv
ity
Not
ass
esse
dA
Es
No
com
plic
atio
ns p
osto
pera
tivel
y, ex
cept
som
e pa
tient
s ha
d m
inor
oed
ema
of t
he p
hary
ngea
l muc
ous
mem
bran
e (r
esol
ved
with
in 5
d)
Aut
hors
’ con
clus
ions
PD
T a
ppea
rs
effe
ctiv
e in
tre
atin
g tu
mou
rs o
f the
pha
rynx
, bu
t la
rger
stu
dies
with
long
er F
U a
re n
eede
dB
rief
stu
dy a
ppra
isal
Thi
s st
udy
used
co
mpa
rato
r tr
eatm
ents
suc
h th
at t
he r
esul
ts
offe
r lit
tle in
sigh
t to
how
PD
T c
ompa
res
with
ot
her
trea
tmen
ts a
djun
ctiv
e to
sur
gery
. The
re
was
spa
rse
repo
rtin
g of
met
hods
and
pat
ient
ch
arac
teri
stic
s, an
d re
sults
wer
e so
met
imes
in
com
plet
e
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.
287
Stud
y de
tails
Popu
lati
on d
etai
lsTr
eatm
ent
deta
ilsR
esul
tsIn
terp
reta
tion
Aut
hors
Vak
ulov
skay
a (2
007)
144
Link
ed p
ublic
atio
ns21
3
Dat
a so
urce
Abs
trac
tC
ount
ry R
ussi
aLa
ngua
ge E
nglis
hSt
udy
desi
gn N
on-R
CT
No.
of p
arti
cipa
nts
Tota
l: 52
Inte
rven
tion:
Not
sta
ted
Com
para
tor:
Not
sta
ted
No.
of r
ecru
itin
g ce
ntre
s N
ot s
tate
dFo
llow
-up
peri
od a
nd
freq
uenc
y N
ot s
tate
d (a
lthou
gh s
urvi
val m
onito
red
up t
o 3
yr)
Trea
tmen
t in
tent
ion
Not
sta
ted
Type
(s)
of c
ance
r an
d hi
stol
ogy
Ora
l can
cer
(SC
C)
Mai
n el
igib
ility
cr
iter
ia N
ot s
tate
dPa
tien
t ch
arac
teri
stic
s Pa
tient
s ha
d tu
mou
rs in
the
ora
l ca
vity
, oro
phar
ynx
or
low
er li
p. Fu
rthe
r pa
tient
ch
arac
teri
stic
s w
ere
not
repo
rted
Con
com
itan
t tr
eatm
ent
Not
sta
ted
Tria
l tre
atm
ents
PD
T w
ith
Phot
osen
se v
s PD
T w
ith R
adac
hlor
inIn
terv
enti
on In
trav
enou
s Ph
otos
ense
(0
.4–0
.8 m
g/kg
) w
ith s
emic
ondu
ctiv
e la
sers
(M
ilon
660,
Bio
spec
672
) at
a
tota
l lig
ht d
ose
of 4
00–6
00 J/
cm2 .
Furt
her
PDT
par
amet
ers
wer
e no
t re
port
edC
ompa
rato
r In
trav
enou
s R
adac
hlor
in
(1.2
–2.4
mg/
kg)
with
sem
icon
duct
ive
lase
rs (
Milo
n 66
0, B
iosp
ec 6
72)
at
a to
tal l
ight
dos
e of
200
–300
J/cm
2 . Fu
rthe
r PD
T p
aram
eter
s w
ere
not
repo
rted
Mor
talit
y N
ot b
roke
n do
wn
by
trea
tmen
t gr
oup
Mor
bidi
ty F
or P
hoto
sens
e a
CR
was
se
en in
57%
of p
atie
nts
and
a PR
in
38%
. For
Rad
achl
orin
a C
R w
as s
een
in
20%
and
a P
R in
50%
QoL
and
ret
urn
to n
orm
al a
ctiv
ity
Not
ass
esse
dA
Es
Mai
n si
de e
ffect
with
Pho
tose
nse
was
incr
ease
d sk
in s
ensi
tivity
to
dire
ct s
unlig
ht, w
ith R
adac
hlor
in s
kin
sens
itivi
ty is
sho
rt t
erm
. No
furt
her
deta
ils w
ere
give
n
Aut
hors
’ con
clus
ions
Our
ex
peri
ence
sho
wed
pro
noun
ced
effic
acy
of P
DT
with
hig
h fu
nctio
nal
and
cosm
etic
effe
cts
for
oral
can
cer
of
diffe
rent
loca
lisat
ions
Bri
ef s
tudy
app
rais
al M
inim
al
repo
rtin
g of
bot
h m
etho
ds a
nd r
esul
ts
mea
ns li
ttle
can
be
dedu
ced
from
thi
s co
nfer
ence
abs
trac
t
NETSCC, Health Technology Assessment Alpha HouseUniversity of Southampton Science ParkSouthampton SO16 7NS, UKEmail: hta@hta.ac.ukwww.hta.ac.uk ISSN 1366-5278
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